Methods for improving the quality of life of a patient with a peanut allergy

ABSTRACT

The present disclosure relates to methods of improving the quality of life of a subject having a peanut allergy. In certain embodiments, the disclosure provides methods for improving the quality of life of a subject having a peanut allergy by administering a peanut composition according to an oral immunotherapy schedule. In certain embodiments, the disclosure provides methods for improving the quality of life of a subject having a peanut allergy by informing the subject they are to be, or are being, administered a peanut composition according to an oral immunotherapy schedule.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the priority benefit of U.S. ProvisionalApplication No. 62/846,481, filed on May 10, 2019; U.S. ProvisionalApplication No. 62/855,384, filed on May 31, 2019; and U.S. ProvisionalApplication No. 62/967,948, filed on Jan. 30, 2020; the disclosures ofwhich are each incorporated herein by reference for all purposes.

FIELD OF THE INVENTION

Described herein are methods for improving the quality of life ofpatients with a peanut allergy.

BACKGROUND OF THE INVENTION

Peanut allergy is an allergic hypersensitivity reaction of the immunesystem to peanut protein. Peanut allergy often develops in childhood andis usually a lifelong affliction without effective treatment. Allergicreactions to peanut can be severe and life threatening, and are a majorsource of severe food-induced anaphylaxis.

Peanut allergy imposes a substantial burden on individuals and theircaregivers/families. The management of peanut allergy involves ongoingmedical care, financial costs, and conscientious avoidance of peanut orother adherence to medical advice. These burdens can manifest in diversemanners, including as anxiety and depressive symptoms. Anxiety regardingthe risk of an allergic event may result in exclusion of peanut-allergicchildren from social events and more. See, for example, Bollinger etal., The impact of food allergy on the daily activities of children andtheir families, Ann. Allergy Asthma Immunol. 96:415-21 (2006).Collectively, these burdens can impact an individual's quality of life(QoL), and even the quality of life of their caregivers or familymembers. See, for example, King et al., Impact of peanut allergy onquality of life, stress and anxiety in the family, Allergy, 64(3):461-8(2009). The burden experienced by individuals having a peanut allergymay be greater than the burden experienced by individuals having otherserious chronic diseases, including type-1 diabetes. See, for example,Avery et al., Assessment of quality of life in children with peanutallergy, Ped. Allergy Immunol. 14:378-82 (2003).

The standard of care for treating peanut allergy generally includesdietary elimination and avoidance of peanuts, education on the signs ofanaphylaxis, and administration of injectable epinephrine in response tosevere allergic reactions with dietary exposure to peanut protein.However, accidental ingestion of peanuts is common, due to difficulty ininterpreting food labels and the presence of undeclared ingredients inunlabeled food. Oral immunotherapy (OIT) is a promising new treatmentfor peanut allergy. See, for example, Bird et al., Efficacy and Safetyof AR101 in Oral Immunotherapy for Peanut Allergy: Results of ARC001; arandomized Double-Blind, Placebo-Controlled Phase 2 Clinical Trial, J.Clin. Immunol. Pract. 6(2):476-485 (2018). Peanut OIT includes exposingpatients to gradually increasing doses of peanut protein to inducedesensitization, which is intended to reduce the risk of a seriousreaction upon accidental exposure to peanut.

SUMMARY OF THE INVENTION

Described herein are methods of improving the quality of life of apatient with a peanut allergy by an oral immunotherapy according to anoral immunotherapy schedule.

In some embodiments, a method of improving the quality of life of apatient with a peanut allergy, comprises: administering to the patient apeanut composition according to an oral immunotherapy schedule.

In some embodiments, the patient is informed that the peanut compositionis being administered. In some embodiments, the patient is informed thatthe peanut composition is being administered to the patient at the startof the oral immunotherapy schedule. In some embodiments, the patient isinformed that the peanut composition is being administered to thepatient during an up-dosing phase of the oral immunotherapy schedule. Insome embodiments, the patient is informed that the peanut composition isbeing administered to the patient during a maintenance phase of the oralimmunotherapy schedule.

In some embodiments, the method further comprises informing the patientthat the peanut composition is being administered to the patient. Insome embodiments, the patient is informed that the peanut composition isbeing administered to the patient prior to the start of the oralimmunotherapy schedule. In some embodiments, the patient is informedthat the peanut composition is being administered to the patient duringan up-dosing phase of an oral immunotherapy schedule. In someembodiments, the patient is informed that the peanut composition isbeing administered to the patient during a maintenance phase of the oralimmunotherapy schedule.

In some embodiments, the quality of life improvement is measured using aquality of life questionnaire (QoLQ). In some embodiments, the QoLQcomprises one or more scored domains of measurement. In someembodiments, the QoLQ is a Food Allergy Quality of Life Questionnaire(FAQLQ). In some embodiments, the FAQLQ is a FAQLQ-child form(FAQLQ-CF), FAQLQ-teen form (FAQLQ-TF), FAQLQ-adult form (FAQLQ-AF), orFAQLQ-parent form (FAQLQ-PF).

In some embodiments, a method of improving the quality of life of apatient with a peanut allergy, as assessed by a quality of lifequestionnaire (QoLQ), comprises administering to the patient a peanutcomposition according to an oral immunotherapy schedule. In someembodiments, the patient is informed that the peanut composition isbeing administered. In some embodiments, the patient is informed thatthe peanut composition is being administered to the patient at the startof the oral immunotherapy schedule. In some embodiments, the patient isinformed that the peanut composition is being administered to thepatient during an up-dosing phase of the oral immunotherapy schedule. Insome embodiments, the patient is informed that the peanut composition isbeing administered during a maintenance phase of the oral immunotherapyschedule. In some embodiments, the method further comprises informingthe patient that the peanut composition is being administered to thepatient. In some embodiments, the method further comprises informing thepatient that the peanut composition is being administered to thepatient, and the patient is informed that the peanut composition isbeing administered to the patient prior to the start of the oralimmunotherapy schedule. In some embodiments, the method furthercomprises informing the patient that the peanut composition is beingadministered to the patient, and the patient is informed that the peanutcomposition is being administered to the patient during an up-dosingphase of an oral immunotherapy schedule. In some embodiments, the methodfurther comprises informing the patient that the peanut composition isbeing administered to the patient, and the patient is informed that thepeanut composition is being administered to the patient during amaintenance phase of the oral immunotherapy schedule. In someembodiments, the QoLQ comprises one or more scored domains ofmeasurement. In some embodiments, the QoLQ is a Food Allergy Quality ofLife Questionnaire (FAQLQ). In some embodiments, the FAQLQ is aFAQLQ-child form (FAQLQ-CF), FAQLQ-teen form (FAQLQ-TF), FAQLQ-adultform (FAQLQ-AF), or FAQLQ-parent form (FAQLQ-PF). In some embodiments,the QoLQ is a Food Allergy Independent Measure (FAIM). In someembodiments, the FAIM is a FAIM-child form (FAIM-CF), FAIM-teen form(FAIM-TF), FAIM-adult form (FAIM-AF), or FAIM-parent form (FAIM-PF). Insome embodiments, the QoLQ is a Pediatric Quality of Life Inventory(PedsQL).

In some embodiments of the preceding methods, the quality of life isimproved for at least 6 months. In some embodiments, the quality of lifeis improved for at least 12 months.

In some embodiments, the one or more scored domains of the QoLQ are eachscored on a scale between 1 and 7, or are each converted to a scorebetween a first score and a second score, wherein the second scoreindicates worse quality of life. In some embodiments, an improvement inthe patient's quality of life is at least 0.5 points in one or moredomains of the QoLQ at a second time point after a period of oralimmunotherapy as compared to an assessment at a first time point beforethe period of oral immunotherapy. In some embodiments, an improvement inthe patient's quality of life is at least 0.5 points in a total score ofthe QoLQ at a second time point after a period of oral immunotherapy ascompared to an assessment at a first time point before the period oforal immunotherapy; wherein the total score is the average of eachdomain score. In some embodiments, the period of oral immunotherapybetween the first time point and the second time point is the up-dosingphase of the oral immunotherapy schedule. In some embodiments, theperiod of oral immunotherapy between the first time point and the secondtime point is at least 1 month of a maintenance therapy of the oralimmunotherapy schedule.

In some embodiments, the quality of life improvement is measured using aquality of life questionnaire (QoLQ). In some embodiments, the QoLQ is aFood Allergy Independent Measure (FAIM). In some embodiments, the FAIMis a FAIM-child form (FAIM-CF), FAIM-teen form (FAIM-TF), FAIM-adultform (FAIM-AF), or FAIM-parent form (FAIM-PF). In some embodiments, animprovement in the patient's quality of life is at least 0.5 points in atotal score of the QoLQ at a second time point after a period of oralimmunotherapy as compared to an assessment at a first time point beforethe period of oral immunotherapy; wherein the total score is the averageof each domain score. In some embodiments, the period of oralimmunotherapy between the first time point and the second time point isthe up-dosing phase of the oral immunotherapy schedule. In someembodiments, the period of oral immunotherapy between the first timepoint and the second time point is at least 1 month of a maintenancetherapy of the oral immunotherapy schedule.

In some embodiments, the quality of life improves after 6 months of theoral immunotherapy schedule.

In some embodiments, the oral immunotherapy schedule comprises anup-dosing phase and a maintenance phase. In some embodiments, the peanutcomposition is administered to the patient during the maintenance phaseon a daily basis. In some embodiments, the maintenance phase is at least3 months. In some embodiments, the peanut composition is administered tothe patient during a maintenance phase of the oral immunotherapyschedule at a dose of about 300 mg peanut protein or more. In someembodiments, the up-dosing phase comprises administering to the patienttwo or more different doses between about 3 mg and about the dose of aninitial maintenance phase dose.

In some embodiments, the oral immunotherapy schedule comprises anup-dosing phase that is between about 3 months and about 2 years inlength.

In some embodiments, the oral immunotherapy schedule further comprisesan initial escalation phase.

In some embodiments, the patient is about 4 years old or older. In someembodiments, the patient is between about 4 years old and about 17 yearsold. In some embodiments, the patient is between about 8 years old andabout 17 years old.

In some embodiments, the method comprises measuring the quality of lifebefore administering to the patient a peanut composition according to anoral immunotherapy schedule. In some embodiments, the method comprisesmeasuring the quality of life after administering to the patient apeanut composition according to an oral immunotherapy schedule. In someembodiments, the method comprises measuring the quality of life afterinforming the patient that the peanut composition is being administered.In some embodiments, the quality of life of the patient is improved asdetermined by a quality of life questionnaire (QoLQ).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows self-reported quality of life results for subjects (ages8-17 years) participating in two peanut OIT clinical trials (PALISADEand an open label extension of the PALISADE trial) as measured by a FoodAllergy Quality of Life Questionnaire (FAQLQ; e.g., FAQLQ-CF orFAQLQ-TF) and by a Food Allergy Independent Measure (FAIM; e.g., FAIM-CFor FAIM-TF) at three time points (left: FAQLQ; right: FAIM). The firsttime point occurred during the screening of the first clinical trial(PALISADE). The second time point (T2) occurred after the completion ofa double-blind placebo controlled food challenge (DBPCFC) administeredat PALISADE exit and before the start of the open label extension. Thethird time point (T3) occurred at the exit of the open label extension.The left panel of FIG. 1 shows mean scores (with 95% confidence intervalindicated) for the FAQLQ total score and for domains of AllergenAvoidance and Dietary Restrictions, Risk of Accidental Exposure, andEmotional Impact. The right panel of FIG. 1 shows mean scores (with 95%confidence interval indicated) for the FAIM total score and forquestions of Expectation of Outcomes, Product Avoidance, and SocialImpact. Both total score results and four of the six domain/questionscore results exceeded the threshold of the minimal clinically importantdifference (MCID) of 0.5 between PALISADE screening and T3, and areindicated by an asterisk above the bars.

FIG. 2 shows proxy-reported quality of life results regarding subjects(ages 4-17 years) participating in two peanut OIT clinical trials(PALISADE and an open label extension of PALISADE) as measured by a FoodAllergy Quality of Life Questionnaire (FAQLQ; e.g., FAQLQ-PF) and by aFood Allergy Independent Measure (FAIM; e.g., FAIM-PF) at three timepoints (left: FAQLQ; right: FAIM). The first time point occurred duringthe screening of the first clinical trial (PALISADE). The second timepoint (T2) occurred after the completion of a double-blind placebocontrolled food challenge (DBPCFC) administered at PALISADE exit andbefore the start of the open label extension. The third time point (T3)occurred at the exit of the open label extension. The left panel of FIG.2 shows mean scores (with 95% confidence interval indicated) for theFAQLQ total score and for domains of Emotional Impact, Food Anxiety, andSocial & Dietary Limitations. The right panel of FIG. 2 shows meanscores (with 95% confidence interval indicated) for the FAIM ChildExpectation of Outcomes (by proxy) and Parent/Caregiver Expectation ofOutcomes. For the Child Expectation of Outcomes (by proxy), parents orcaregivers of children age 13-17 were not tested for this question. TheParent/Caregiver Expectation of Outcomes question exceeded the minimumclinically important difference (MCID) between PALISADE screening andT3, and is indicated by an asterisk above the bars.

FIG. 3 shows the change in quality of life of various subjects from thescreening of a first peanut OIT clinical trial (PALISADE) to the exit ofthe open label extension of PALISADE, including a time point betweenPALISADE and the open label extension. Circular points indicate mean(with 95% confidence interval indicated) change in the Food AllergyQuality of Life Questionnaire (FAQLQ) total scores either by self-report(e.g., FAQLQ-CF or FAQLQ-TF) or by proxy-report (e.g., FAQLQ-PF).Triangular points indicate mean (with 95% confidence interval indicated)change in Food Allergy Independent Measure (FAIM) total scores either byself-report (e.g., FAIM-CF or FAIM-TF) or by proxy-report (e.g.,FAIM-PF). Solid and dashed lines indicate “yes” and “no,” respectively,with respect to whether the particular subjects tolerated at least 600mg peanut protein at a time point in-between the two clinical trials(i.e., the PALISADE exit) as measured in a double-blindplacebo-controlled food challenge, whether the subjects experiencedsystemic allergic reactions during either the first clinical trial(PALISADE) or the open label extension, and whether subjects reportedusing adrenaline during the first clinical trial (PALISADE) or the openlabel extension. The dashed vertical line (+/−0.5 score change)indicates the minimum clinically important difference (MCID) per the QoLinstrument.

FIG. 4 shows FAQLQ and FAIM total scores and domain scores as reportedby participants aged 8-12 years from a European clinical trial of AR101at active group screening (first line of each total score or domainscore), active group exit (second line of each total score or domainscore), placebo group screening (third line of each total score ordomain score), and placebo group exit (fourth line of each total scoreor domain score).

FIG. 5 shows FAQLQ and FAIM total scores and domain scores as reportedby participants aged 13-17 years from a European clinical trial of AR101at active group screening (first line of each total score or domainscore), active group exit (second line of each total score or domainscore), placebo group screening (third line of each total score ordomain score), and placebo group exit (fourth line of each total scoreor domain score).

FIG. 6 shows proxy-reported FAIM scores across domains as reported bycaregivers of participants aged 4-12 years from a European clinicaltrial of AR101 at active group screening (first line of each domain),active group exit (second line of each domain), placebo screening (thirdline of each domain), and placebo exit (fourth line of each domain).

DETAILED DESCRIPTION OF THE INVENTION

Described herein are methods of improving the quality of life of apatient with a peanut allergy. The methods can include administering tothe patient a peanut composition according to an oral immunotherapyschedule. It has been discovered that subjects who suffer a reducedquality of life as a result of a peanut allergy may have improvedquality of life by treatment with a peanut composition according to anoral immunotherapy schedule. Across multiple large-scale clinical trialstesting the efficacy of an investigational peanut protein oral biologicdrug AR101 in oral immunotherapy, significant improvements across eachof the active cohorts in subject-reported and proxy-reported quality oflife were observed after initial desensitization and periods ofmaintenance therapy. These substantial improvements across cohortsindicate that an individual receiving the treatment described herein islikely to have an improvement in quality of life.

A subject's quality of life may be improved by informing the subjectthey are to be administered, or are being administered, a peanutcomposition according to an oral immunotherapy schedule for thetreatment of peanut allergy. Knowledge of treatment with an activetherapeutic (i.e., the peanut composition), as opposed to beingadministered a composition in a blinded study without knowledge oftreatment, can result in a quality of life improvement. Oralimmunotherapy involves dosing with peanut protein by the same route thataccidental dietary exposure occurs (i.e., oral ingestion). Oncedesensitization has been achieved, oral immunotherapy may thereforeprovide additional certainty to the patient, and/or their caregiver,that the patient is protected from accidental exposure to peanutprotein, compared to other immunotherapy methods, such as those based ondermal exposure or injection. This effect may be independent of actualdesensitization. Every dose of peanut protein according to an oralimmunotherapy schedule after the patient has been informed they arebeing administered the peanut composition may reinforce the patient'sconfidence that they are desensitized to accidental exposure, and thusimprove the patient's quality of life over time. Thus, the methods ofimproving the quality of life of a patient described herein can includeadministering the peanut composition to patients that have knowledge ofthe treatment, (i.e., are informed that they are receiving the peanutcomposition and not a placebo). The patient may be informed of activetreatment prior to the start of the oral immunotherapy schedule orduring the oral immunotherapy schedule (such as during an up-dosingphase or a maintenance phase of the oral immunotherapy schedule). Insome embodiments, the method includes informing the patient of activetreatment (i.e., that the peanut composition is being administered tothe patient).

Oral immunotherapy (OIT) is a method of inducing desensitization to anallergen in a subject by regular exposure of the subject to increasingdoses of the allergen. For peanut allergy, protocols for OIT typicallyinvolve an up-dosing phase (also called a build-up phase) and amaintenance phase. The OIT can further include an initial escalationphase, although this phase is optional and not required for treatment.The initial escalation phase involves exposure to small doses of peanutprotein under clinical supervision to determine the sensitivity of thepatient to the peanut protein. This initial escalation phase generallyoccurs over the course of several (e.g., three or more) hours to twodays. These small doses are increased until the subject reaches a goaldose or a highest tolerated dose for the initial escalation phase. Thesubject then usually begins an up-dosing phase beginning with thehighest tolerated dose administered in the initial escalation phase or aslightly lower dose, and escalating through a series of doses in anup-dosing phase. Additionally, peanut OIT includes a maintenance phaseinvolving continued administration of peanut protein for a period oftime. One goal of oral immunotherapy is establishing a desensitizedstate, wherein the subject being treated is less likely to suffer asevere or life-threatening allergic reaction upon accidental exposure topeanut protein.

Subjects having a peanut allergy may suffer a reduced quality of life,and their quality of life may be improved by the methods describedherein.

Definitions

As used herein, the singular forms “a,” “an,” and “the” include theplural references unless the context clearly dictates otherwise.

Reference to “about” a value or parameter herein includes (anddescribes) variations that are directed to that value or parameter perse. For example, description referring to “about X” includes descriptionof “X”.

The term “desensitized” is used herein to refer to an increased reactionthreshold to a food allergen by a subject as a result of an oralimmunotherapy for the food allergen. Desensitization to a food allergencan be tested using methods known in the art, including an oral foodchallenge. Desensitization may be partial, wherein the subject toleratesan increased amount of the food allergen compared to prior to treatment,but still reacts to higher doses of the food allergen; or thedesensitization may be complete, wherein the patient tolerates alltested doses of the food allergen.

The phrase “quality of life” as used herein is synonymous with“disease-related quality of life” and “health-related quality of life,”and refers to the portion(s) of a subject's life affected by a foodallergy and/or affected by its treatment.

The terms “effective,” “efficacy,” or “effectiveness” are used herein torefer to the ability of a therapy to induce immune modulation, such asdesensitization, or sustain a desired immune state, such as adesensitized state, unless otherwise indicated.

As used herein, “maintenance phase” refers to a phase of a peanutprotein oral immunotherapy that includes administration of peanutprotein (i.e., a maintenance dose) to the patient, and occurs aftercompletion of the up-dosing phase.

As used herein, a “mild allergic adverse event” refers to an observed orexperienced OIT-treatment-related allergic adverse event associated withtransient discomfort, but does not require immediate medicalintervention such as hospitalization or epinephrine, and does notsubstantially interfere with daily activities.

As used herein, a “moderate allergic adverse event” refers to anobserved or experienced OIT-treatment-related allergic adverse eventthat is associated with discomfort of a sufficient degree to interferewith daily activities and that may prompt medical intervention and/oradditional observation.

As used herein, “daily” dosing means administering a dose on eachconsecutive calendar day. The dose may be administered as a singleportion on the calendar day, or subdivided into multiple portionsadministered within the same calendar day.

As used herein, the phrase “serious allergic adverse event” refers to anobserved or experienced OIT-treatment-related allergic adverse eventleading to anaphylaxis that requires hospitalization and/oradministration of epinephrine or other life-saving medical intervention.

The term “subject” or “patient” is used synonymously and interchangeablyherein to describe a human of any age.

A subject “tolerates” a dose when the dose is administered to thesubject without any moderate or severe allergic adverse event. A subjectis considered to tolerate the dose even if a mild allergic adverse eventis observed or experienced.

The terms “treat,” “treating,” and “treatment” are used synonymouslyherein to refer to any action providing a benefit to a subject afflictedwith a disease state or condition, including improvement in thecondition through lessening, inhibition, suppression, or elimination ofat least one symptom; delay in progression of the disease; delay inrecurrence of the disease; inhibition of the disease; or partially orfully reducing a response or reaction to an allergen.

An “up-dosing phase” refers to a phase of an oral immunotherapycharacterized by a series of increasing food allergen doses, beginningwith administration of a dose of food allergen lower than the highestdose administered to the patient during the oral immunotherapy, andending when the highest dose administered to the patient during the oralimmunotherapy is achieved.

It is understood that aspects and variations of the invention describedherein include “consisting” and/or “consisting essentially of” aspectsand variations.

When a range of values is provided, it is to be understood that eachintervening value between the upper and lower limit of that range, andany other stated or intervening value in that states range, isencompassed within the scope of the present disclosure. Where the statedrange includes upper or lower limits, ranges excluding either of thoseincluded limits are also included in the present disclosure.

The section headings used herein are for organization purposes only andare not to be construed as limiting the subject matter described. Thedescription is presented to enable one of ordinary skill in the art tomake and use the invention and is provided in the context of a patentapplication and its requirements. Various modifications to the describedembodiments will be readily apparent to those persons skilled in the artand the generic principles herein may be applied to other embodiments.Thus, the present invention is not intended to be limited to theembodiment shown but is to be accorded the widest scope consistent withthe principles and features described herein.

The disclosures of all publications, patents, and patent applicationsreferred to herein are each hereby incorporated by reference in theirentireties. To the extent that any reference incorporated by referenceconflicts with the instant disclosure, the instant disclosure shallcontrol.

Methods of Improving Quality of Life

The quality of life of a patient having a peanut allergy may be improvedby administering to the patient a peanut composition according to anoral immunotherapy schedule. In some embodiments, the quality of life ofa patient having a peanut allergy may be improved by informing thepatient that they are being administered, or going to be administered, apeanut composition according to an oral immunotherapy schedule. In someembodiments, the quality of life of a patient having a peanut allergymay be improved by instructing the patient's caregiver to inform thepatient that they are being, or going to be, administered a peanutcomposition according to an oral immunotherapy schedule.

The subject may be informed they are to be administered, or are beingadministered, a peanut composition according to an oral immunotherapyschedule, or the subject's caregiver may be informed that the subject isto be administered, or is being administered, a peanut compositionaccording to an oral immunotherapy schedule, at any time before orduring the oral immunotherapy. In some embodiments, the subject isinformed, or the subject's caregiver is instructed to inform thesubject, before the beginning of the oral immunotherapy schedule. Insome embodiments, the subject is informed, or the subject's caregiver isinstructed to inform the subject, before the initiation of the up-dosingphase of the oral immunotherapy schedule. In some embodiments, thesubject is informed, or the subject's caregiver is instructed to informthe subject, during the up-dosing phase of the oral immunotherapyschedule. In some embodiments, the subject is informed, or the subject'scaregiver is instructed to inform the subject, after the up-dosing phaseof the oral immunotherapy schedule. In some embodiments, the subject isinformed, or the subject's caregiver is instructed to inform thesubject, during a maintenance phase of the oral immunotherapy schedule.In some embodiments, the subject is informed, or the subject's caregiveris instructed to inform the subject, after at least a month ofmaintenance therapy of the oral immunotherapy schedule, such as at least2 months, at least 3 months, at least 6 months, and at least 12 monthsof maintenance therapy of the oral immunotherapy.

Before, during, or after an oral immunotherapy, a subject may undergo aquality of life assessment. Peanut allergy affects quality of lifethrough allergic reactions to peanut protein. However, even absentallergic reactions, subjects having a peanut allergy suffer impairedquality of life, including from the fear of allergic reactions, thefinancial burden of the allergy, the social restrictions of the allergy,and more. Subjects and their caregivers must devote significant timevetting and validating food selections, for example by reading foodlabels, inquiring of ingredients in unlabeled food, or avoiding foodprepared in environments with potential cross-contamination. Subjectsand their caregivers may experience anxiety over these burdens, whichcan manifest further as depressive symptoms. Subjects may avoid livingalone or even eating alone for fear of a rapid onset allergic reaction.Together, these effects reduce a subject's quality of life.

Methods of measuring quality of life, such as disease-related QoL,before, during, or after OIT have been, and may be, developed andvalidated for the measurement of quality of life in subjects with a foodallergy, such as a peanut allergy. The most common methods of assessingquality of life employ questionnaires designed to assess one or moredomains, across one or more issues each, of the burden imposed by foodallergy, such as peanut allergy, in qualitative and/or quantitativeterms. Exemplary questionnaires are generally (1) valid, meaning thatthe part(s) of quality of life that are being measured relate to thefood allergy; (2) reproducible, meaning that questionnaires taken undersimilar conditions are equivalent, and may generally produce similarresults absent a change in the food allergy burden or treatment burden;(3) responsive, meaning that changes in the food allergy burden and/ortreatment burden are detected and/or detectible; and (4) interpretable,meaning that scored changes are clinically significant, as determined bythe questionnaire's minimal clinical important difference (MCID).

An improvement in a subject's quality of life involves a change betweenat least two points in time. Further, an improvement is understood withrespect to a particular instrument (such as a particular quality of lifequestionnaire or other QoL assessment). For example, if a subject'squality of life is assessed by a quality of life questionnaire, then animprovement is an improvement in the score of that same quality of lifequestionnaire, such as an improvement in a particular domain or animprovement in the total score of said questionnaire. In someembodiments, the improvement is clinically significant, such as equal toor greater than the questionnaire's minimal clinical importantdifference (MCID). In some embodiments, the improvement is a change in adomain score, or a total score, of a quality of life questionnairebetween one time point, such as a baseline measurement, to a second timepoint.

In some embodiments. a skilled medical provider, such as a physician,nurse, allergist, or other professional trained in the field of allergytreatment, may select a QoL assessment instrument appropriate for asubject to be treated, or being treated, by an oral immunotherapy for afood allergy, such as a peanut allergy. Preferably, QoL assessmentinstruments are age-appropriate and validated for the particular agerange of the subject. For young subjects, a proxy-report (such as one tobe completed by the subject's caregiver regarding the subject having apeanut allergy) may be required or may compliment a self-report, forexample in subjects under the age of 12. For subjects 6-, 7-, or8-years-old or older, a self-report alone may be, but is not always,sufficient. In some embodiments, assessment instruments may be validatedfor the native language of the subject (for self-reports) and/or thesubject's caregiver (for proxy-reports). In some embodiments, assessmentinstruments may be culturally validated, for example, validated in thecountry or region where the subject (for self-reports) and/or thesubject's caregiver (for proxy-reports) reside.

In some embodiments, quality of life may be assessed by quality of lifequestionnaires (QoLQ), such as food allergy-specific QoLQs. In someembodiments, the food allergy-specific QoLQ is a peanut allergy-specificQoLQ. A QoLQ is typically divided into one or more domains, wherein eachdomain relates to a category of physical, mental, emotional, or socialfunctioning or well-being. The domains of a QoLQ may comprise one ormore issues. The QoLQ may score one or more domains and/or one or moreissues, individually and/or in the aggregate. Exemplary domains and/orissues covered may include, but are not limited to: bullying, teasing,family, family events, school, school events, social, social events,field trips, parties, sleepovers, playing at friends' houses, timeemployed to prepare foods, physical state, mental state, emotionalstate, expectations of outcome, perceived risk, parental anxiety,parental distress, psychosocial impact, parental coping, family support,social precaution, food allergen identification, emotional impact,food-related anxiety, social restrictions, allergen avoidance, dietaryrestriction, risk of accidental exposure, fear, perception,independence, and/or burden of carrying adrenaline. In some embodiments,the domain and/or issues measured by the QoLQ comprise any domain and/orissue validated to relate to the burden of having a food allergy and/orthe treatment of a food allergy. In some embodiments, the domain and/orissues measured by the QoLQ comprise any domain and/or issue validatedto relate to the burden of having a food allergy that is a peanutallergy and/or the treatment of a food allergy that is a peanut allergy.

In some embodiments, quality of life of a subject having a peanutallergy may be assessed by administering one or more QoLQs to a subjecthaving a peanut allergy to measure said subject's quality of life. Insome embodiments, quality of life of a subject having a peanut allergymay be assessed by proxy by administering one or more QoLQs to asubject's caregiver to measure said subject's quality of life. In someembodiments, quality of life of a subject having a peanut allergy may beassessed by administering one or more QoLQs to a subject having a peanutallergy and by administering one or more QoLQs to a subject's caregiverto measure said subject's quality of life. In some embodiments, asubject's caregiver is any individual aware of the physiological,emotional, financial, and/or physical burden of a peanut allergy on saidsubject. In some embodiments, a subject's caregiver is a family member(such as a parent, grandparent, sibling, aunt, uncle, cousin, etc.) orother guardian (such as a legally appointed guardian).

In some embodiments, the quality of life of a subject having a peanutallergy may be assessed by administering one or more QoLQs to measure asubject's quality of life. In some embodiments, the one or more QoLQs tomeasure a subject's quality of life comprise one or more QoLQs selectedfrom: the Food Allergy Quality of Life-Parental Burden questionnaire(FAQL-PB), the Food Allergy Impact Scale (FAIS), the Food AllergyIndependent Measure (FAIM), the Food Allergy Independent Measure childform (FAIM-CF), the Food Allergy Independent Measure teen form(FAIM-TF), the Food Allergy Independent Measure adult form (FAIM-AF),the Food Allergy Independent Measure parent form (FAIM-PF), the FoodAllergy Parent Questionnaire (FAPQ), the Child Health QuestionnaireParental Form (CHQ-PF), the Food Allergy Self-Efficacy Scale for Parents(FASE-P), the Pediatric Allergic Disease Quality of Life Questionnaire(PADQLQ), the Food Allergy Quality of Life Questionnaire-Parent Form(FAQLQ-PF), the Food Allergy Quality of Life Questionnaire-Child Form(FAQLQ-CF), the Food Allergy Quality of Life Questionnaire-Teenager Form(FAQLQ-TF), the Food Allergy Quality of Life Assessment Tool forAdolescents (FAQL-teen), the You and Your Food Allergy questionnaire,the Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF),the 36-Item Short Form Health Survey (SF-36), a EuroQol EQ-5D, such asthe EuroQol 5D Youth (EQ-5D-Y) or 5-level EQ-5D (EQ-5D-5L), the HospitalAnxiety and Depression Scale (HADS), the Allergy to Peanuts ImPactingEmotions and Life (APPEAL) survey, and the Pediatric Quality of LifeInventory (PedsQL). In some embodiments, the one or more QoLQs comprisea FAQLQ, such as FAQLQ-CF, FAQLQ-TF, FAQLQ-AF, or FAQLQ-PF. In someembodiments, the one or more QoLQs comprises a self-reported FAQLQ-CF,FAQLQ-TF, or FAQLQ-AF. In some embodiments, the one or more QoLQscomprises a proxy-reported FAQLQ-PF. In some embodiments, the one ormore QoLQs comprise a self-reported FAQLQ-CF, FAQLQ-TF, FAQLQ-AF and aproxy-reported FAQLQ-PF. In some embodiments, the one or more QoLQscomprise a FAIM, such as a FAIM-CF, FAIM-TF, FAIM-AF, or FAIM-PF.

A QoLQ typically comprises one or more scored domains, with each domainreflecting an aspect or category related to a subject's quality of life.In some embodiments, the QoLQ will assign a numerical score to eachdomain along a scale. Scores may be on any scale, with a first scoreassociated with a better quality of life and a second score associatedwith a worse quality of life. For example, the scale may be between 1and 5, between 1 and 6, between 1 and 7, or any other selected values.In accordance with some scales, a higher score can be used to indicate aworse quality of life. A total score, an aggregate score, and/or amulti-domain score may also be assessed based on the averaged score of aplurality of domains of a QoLQ. In some embodiments, a domain and/ortotal score of a QoLQ may be converted to a common scale, such as ascore between 1 and 7, wherein 7 is associated with worse quality oflife, or a score between a first score and a second score, wherein asecond score is associated with worse quality of life.

The QoLQ administered should be suitable to the subjects and/or theircaregivers. In some embodiments, the one or more QoLQs administered aretranslated to a language understood by the subject and/or theircaregiver. In some embodiments, the one or more QoLQs administered arevalidated to ensure lingual and cultural suitability for the subjectand/or their caregiver.

In some embodiments, the quality of life of a subject is assessed, atleast in part, by proxy by administering a QoLQ regarding the subject tothe subject's caregiver. In some embodiments, the QoLQ administered to asubject's caregiver to assess the subject's QoL is a QoLQ designed forproxy assessment of a subject having a food allergy, such as a peanutallergy. In a non-limiting exemplary embodiment, the QoLQ administeredto a subject's caregiver to assess the subject's QoL by proxy is theFAQLQ-PF.

The quality of life of a subject having a peanut allergy may be improvedby administering a peanut composition to the subject according to anoral immunotherapy schedule and/or informing the subject they are to beadministered, or are being administered, a peanut composition accordingto an oral immunotherapy schedule. Said improvement in the subject'squality of life may persist (including continuing to further improve)for a period of time after the improvement as the subject continues tobe administered (and/or is aware that they will continue to beadministered) a peanut composition according to an oral immunotherapyschedule. The improvement may persist, including continuing to improve,even if the subject's physiological sensitivity to peanut protein doesnot further improve. Thus, in some embodiments, the subject's quality oflife is improved for at least any of about 1 month, 3 months, 6 months,9 months, 12 months, 18 months, 24 months, 36 months, 48 months, or 60months. In some embodiments, the subject's quality of life is improvedfor at least any of about 1 month, 3 months, 6 months, 9 months, 12months, 18 months, 24 months, 36 months, 48 months, or 60 months whilethe subject continues to be administered a peanut composition accordingto an oral immunotherapy schedule. In some embodiments, the subject'squality of life is improved for at least any of about 1 month, 3 months,6 months, 9 months, 12 months, 18 months, 24 months, 36 months, 48months, or 60 months after the subject has achieved a peakdesensitization to peanut protein (such as by measured by an oral foodchallenge).

In some embodiments, the quality of life of a subject having a peanutallergy is improved by administering a peanut composition to the subjectaccording to an oral immunotherapy schedule and/or informing the subjectthey are to be administered, or are being administered, a peanutcomposition according to an oral immunotherapy schedule. In someembodiments, the improvement in quality of life is determined byimprovement in one or more domains of one or more QoLQs, wherein eachdomain is scored. In some embodiments, the score for each domain isconverted to a score between a first score and a second score, whereinthe second score indicates a worse quality of life. In some embodiments,quality of life is assessed at a first time point and a second timepoint. In some embodiments, the improvement in quality of life of thesubject between the first time point and the second time point is atleast a minimal clinically important difference. In some embodiments,the first time point is before the oral immunotherapy. In someembodiments, the first time point is before the up-dosing phase of theoral immunotherapy. In some embodiments, the first time point is duringthe up-dosing phase of the oral immunotherapy. In some embodiments, thefirst time point is during the maintenance phase of the oralimmunotherapy. In some embodiments, the subject is informed that theyare to be administered a peanut composition according to an oralimmunotherapy schedule before the first time point. In some embodiments,the subject is informed that they are to be administered a peanutcomposition according to an oral immunotherapy schedule at the firsttime point. In some embodiments, a period of oral immunotherapy betweenthe first time point and the second time point comprises the up-dosingphase of the oral immunotherapy schedule. In some embodiments, a periodof oral immunotherapy between the first time point and the second timepoint comprises at least 1 month of maintenance therapy, such as atleast 2 months, at least 3 months, at least 4 months, at least 5 months,at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the improvement in quality of life is determined byimprovement in one or more domains of one or more QoLQs, wherein eachdomain is scored. In some embodiments, at least one domain is a measureof anxiety. In some embodiments, at least one domain is a measure ofemotional impact, such as the emotional impact of having an allergyand/or the emotional impact of the treatment of an allergy. In someembodiments, at least one domain is a measure of social impact, such aslimitations of social interaction and/or participation. In someembodiments, at least one domain is a measure of dietary impact, such ascaloric intake, dietary diversity, and/or dietary exclusion. In someembodiments, at least one domain is a measure of expectations, such asexpectations of treatment success and/or expectations regarding thefuture incidence of allergic reactions and/or expectations regarding theimprovement of the disease condition. In some embodiments, the score foreach domain is converted to a score between a first score and a secondscore, wherein the second score indicates a worse quality of life. Insome embodiments, quality of life is assessed at a first time point anda second time point. In some embodiments, the score at the first timepoint is equal to or greater than the mid-point of the scale. Forexample, in an exemplary embodiment, each domain is scored on a scalefrom 1 to 7, wherein 7 indicates a worse quality of life, and the scoreof one or more domains at the first time point is equal to or greaterthan the mid-point of the scale, which is equal to or greater than 4. Insome embodiments, the score of one or more domains at the second timepoint is less than the mid-point of the scale. For example, in anexemplary embodiment, each domain is scored on a scale from 1 to 7,wherein 7 indicates a worse quality of life, and the score of one ormore domains at the second time point is less than the mid-point of thescale, which is less than 4. In some embodiments, the first time pointis before the oral immunotherapy. In some embodiments, the first timepoint is before the up-dosing phase of the oral immunotherapy. In someembodiments, the first time point is during the up-dosing phase of theoral immunotherapy. In some embodiments, the first time point is duringthe maintenance phase of the oral immunotherapy. In some embodiments,the subject is informed that they are to be administered a peanutcomposition according to an oral immunotherapy schedule before the firsttime point. In some embodiments, the subject is informed that they areto be administered a peanut composition according to an oralimmunotherapy schedule at the first time point. In some embodiments, aperiod of oral immunotherapy between the first time point and the secondtime point comprises the up-dosing phase of the oral immunotherapyschedule. In some embodiments, a period of oral immunotherapy betweenthe first time point and the second time point comprises at least 1month of maintenance therapy, such as at least 2 months, at least 3months, at least 4 months, at least 5 months, at least 6 months, or atleast 12 months of maintenance therapy.

In some embodiments, the quality of life of a subject having a peanutallergy is improved by administering a peanut composition to the subjectaccording to an oral immunotherapy schedule and/or informing the subjectthey are to be administered, or are being administered, a peanutcomposition according to an oral immunotherapy schedule. In someembodiments, the improvement in quality of life is determined byimprovement in the total score of one or more QoLQs, wherein the totalscore is the average of one or more domains of a QoLQ. In someembodiments, the total score is converted to a score between a firstscore and a second score, wherein the second score indicates a worsequality of life. In some embodiments, quality of life is assessed at afirst time point and a second time point. In some embodiments, theimprovement in quality of life of the subject between the first timepoint and the second time point is at least a minimal clinicallyimportant difference. In some embodiments, the first time point isbefore the oral immunotherapy. In some embodiments, the first time pointis before the up-dosing phase of the oral immunotherapy. In someembodiments, the first time point is during the up-dosing phase of theoral immunotherapy. In some embodiments, the first time point is duringthe maintenance phase of the oral immunotherapy. In some embodiments,the subject is informed that they are to be administered a peanutcomposition according to an oral immunotherapy schedule before the firsttime point. In some embodiments, the subject is informed that they areto be administered a peanut composition according to an oralimmunotherapy schedule at the first time point. In some embodiments, aperiod of oral immunotherapy between the first time point and the secondtime point comprises the up-dosing phase of the oral immunotherapyschedule. In some embodiments, a period of oral immunotherapy betweenthe first time point and the second time point comprises at least 1month of maintenance therapy, such as at least 2 months, at least 3months, at least 4 months, at least 5 months, at least 6 months, or atleast 12 months of maintenance therapy.

In some embodiments, the improvement in quality of life is determined byimprovement in the total score of one or more QoLQs, wherein the totalscore is the average of one or more domains of a QoLQ. In someembodiments, the total score is converted to a score between a firstscore and a second score, wherein the second score indicates a worsequality of life. In some embodiments, quality of life is assessed at afirst time point and a second time point. In some embodiments, the scoreat the first time point is equal to or greater than the mid-point of thescale. For example, in an exemplary embodiment, the total score isscored on a scale from 1 to 7, wherein 7 indicates a worse quality oflife, and the total score at the first time point is equal to or greaterthan the mid-point of the scale, which is equal to or greater than 4. Insome embodiments, the total score at the second time point is less thanthe mid-point of the scale. For example, in an exemplary embodiment,each domain is scored on a scale from 1 to 7, wherein 7 indicates aworse quality of life, and the score of one or more domains at thesecond time point is less than the mid-point of the scale, which is lessthan 4. In some embodiments, the first time point is before the oralimmunotherapy. In some embodiments, the first time point is before theup-dosing phase of the oral immunotherapy. In some embodiments, thefirst time point is during the up-dosing phase of the oralimmunotherapy. In some embodiments, the first time point is during themaintenance phase of the oral immunotherapy. In some embodiments, thesubject is informed that they are to be administered a peanutcomposition according to an oral immunotherapy schedule before the firsttime point. In some embodiments, the subject is informed that they areto be administered a peanut composition according to an oralimmunotherapy schedule at the first time point. In some embodiments, aperiod of oral immunotherapy between the first time point and the secondtime point comprises the up-dosing phase of the oral immunotherapyschedule. In some embodiments, a period of oral immunotherapy betweenthe first time point and the second time point comprises at least 1month of maintenance therapy, such as at least 2 months, at least 3months, at least 4 months, at least 5 months, at least 6 months, or atleast 12 months of maintenance therapy.

In some embodiments, the quality of life of a subject having a peanutallergy is determined by one or more QoLQs, wherein at least one QoLQ isa FAQLQ-CF. In some embodiments, the total score of a FAQLQ-CFadministered to a subject having a peanut allergy at a first time pointbefore an oral immunotherapy or during the up-dosing phase of an oralimmunotherapy is 4 or higher. In some embodiments, the score of one ormore domains of a FAQLQ-CF administered to a subject having a peanutallergy at a first time point before an oral immunotherapy or during theup-dosing phase of an oral immunotherapy is 4 or higher, such as a scoreof 4 or higher in the Allergen Avoidance and Dietary Restrictionsdomain, a score of 4 or higher in the Emotional Impact domain, and/or ascore of 4 or higher in the Risk of Accidental Exposure domain. In someembodiments, the total score of a FAQLQ-CF administered to a subjectwith a peanut allergy after at a second time point after a period oforal immunotherapy as compared to the total score of a FAQLQ-CFadministered to said subject at a first time point before the oralimmunotherapy is improved by at least 0.5 points, such as at least 1point, at least 2 points, at least 3 points, or at least 4 points. Insome embodiments, the total score of a FAQLQ-CF administered to asubject with a peanut allergy at a second time point after a period oforal immunotherapy as compared to the total score of a FAQLQ-CFadministered to said subject at a first time point during the up-dosingphase of an oral immunotherapy is improved by at least 0.5 points, suchas at least 1 point, at least 2 points, at least 3 points, or at least 4points. In some embodiments, the score of a domain of a FAQLQ-CFadministered to a subject having a peanut allergy is improved by atleast 0.5 points, such as at least 0.5 points in the Allergen Avoidanceand Dietary Restrictions domain, at least 0.5 points in the EmotionalImpact domain, and/or at least 0.5 points in the Risk of AccidentalExposure domain at a second time point after a period of oralimmunotherapy as compared to the score in each domain at the first timepoint before the oral immunotherapy or during the up-dosing phase of theoral immunotherapy. In some embodiments, the subject is informed theyare to be administered a peanut composition before the oralimmunotherapy. In some embodiments, the period of oral immunotherapybetween the first time point and the second time point comprises anup-dosing phase. In some embodiments, the period of oral immunotherapybetween the first time point and the second time point comprises atleast 1 month of maintenance therapy, such as at least 2 months, atleast 3 months, at least 4 months, at least 5 months, at least 6 months,or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a subject having a peanutallergy is determined by one or more QoLQs, wherein at least one QoLQ isa FAQLQ-CF. In some embodiments, the total score of a FAQLQ-CFadministered to a subject having a peanut allergy at a first time pointbefore being informed they are to be administered, or are beingadministered, a peanut composition according to an oral immunotherapyschedule is 4 or higher. In some embodiments, the score of one or moredomains of a FAQLQ-CF administered to a subject having a peanut allergyat a first time point before being informed they are to be administered,or are being administered, a peanut composition according to an oralimmunotherapy schedule is 4 or higher, such as a score of 4 or higher inthe Allergen Avoidance and Dietary Restrictions domain, a score of 4 orhigher in the Emotional Impact domain, and/or a score of 4 or higher inthe Risk of Accidental Exposure domain. In some embodiments, the totalscore of a FAQLQ-CF administered to a subject with a peanut allergy at asecond time point after a period after being informed they are to beadministered, or are being administered, a peanut composition accordingto an oral immunotherapy schedule as compared to the total score of aFAQLQ-CF administered to said subject at a first time point before beinginformed is improved by at least 0.5 points, such as at least 1 point,at least 2 points, at least 3 points, or at least 4 points. In someembodiments, the score of a domain of a FAQLQ-CF administered to asubject having a peanut allergy is improved by at least 0.5 points, suchas at least 0.5 points in the Allergen Avoidance and DietaryRestrictions domain, at least 0.5 points in the Emotional Impact domain,and/or at least 0.5 points in the Risk of Accidental Exposure domain ata second time point after being informed they are to be administered, orare being administered, a peanut composition according to an oralimmunotherapy schedule as compared to the score in each domain at a timepoint before being informed. In some embodiments, the period of oralimmunotherapy between a first time point and a second time point is atleast one month of therapy. In some embodiments, the period between afirst time point and a second time point comprises an up-dosing phase ofthe oral immunotherapy. In some embodiments, the period of oralimmunotherapy between a first time point and a second point is at least1 month of maintenance therapy, such as at least 2 months, at least 3months, at least 4 months, at least 5 months, at least 6 months, or atleast 12 months of maintenance therapy.

In some embodiments, the quality of life of a subject having a peanutallergy is determined by one or more QoLQs, wherein at least one QoLQ isa FAQLQ-TF. In some embodiments, the total score of a FAQLQ-TFadministered to a subject having a peanut allergy at a first time pointbefore an oral immunotherapy or during the up-dosing phase of an oralimmunotherapy is 4 or higher. In some embodiments, the score of one ormore domains of a FAQLQ-TF administered to a subject having a peanutallergy at a first time point before an oral immunotherapy or during theup-dosing phase of an oral immunotherapy is 4 or higher, such as a scoreof 4 or higher in the Allergen Avoidance and Dietary Restrictionsdomain, a score of 4 or higher in the Emotional Impact domain, and/or ascore of 4 or higher in the Risk of Accidental Exposure domain. In someembodiments, the total score of a FAQLQ-TF administered to a subjectwith a peanut allergy at a second time point after a period of oralimmunotherapy as compared to the total score of a FAQLQ-TF administeredto said subject at a first time point before the oral immunotherapy isimproved by at least 0.5 points, such as at least 1 point, at least 2points, at least 3 points, or at least 4 points. In some embodiments,the total score of a FAQLQ-TF administered to a subject with a peanutallergy at a second time point after a period of oral immunotherapy ascompared to the total score of a FAQLQ-TF administered to said subjectat a first time point during the up-dosing phase of an oralimmunotherapy is improved by at least 0.5 points, such as at least 1point, at least 2 points, at least 3 points, or at least 4 points. Insome embodiments, the score of a domain of a FAQLQ-TF administered to asubject having a peanut allergy is improved by at least 0.5 points, suchas at least 0.5 points in the Allergen Avoidance and DietaryRestrictions domain, at least 0.5 points in the Emotional Impact domain,and/or at least 0.5 points in the Risk of Accidental Exposure domain ata second time point after a period of oral immunotherapy as compared tothe score in each domain at a first time point before the oralimmunotherapy or during the up-dosing phase of the oral immunotherapy.In some embodiments, the subject is informed they are to be administereda peanut composition before the oral immunotherapy. In some embodiments,the period of oral immunotherapy between the first time point and thesecond time point comprises an up-dosing phase. In some embodiments, theperiod of oral immunotherapy between a first time point and a secondtime point comprises at least 1 month of maintenance therapy, such as atleast 2 months, at least 3 months, at least 4 months, at least 5 months,at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a subject having a peanutallergy is determined by one or more QoLQs, wherein at least one QoLQ isa FAQLQ-TF. In some embodiments, the total score of a FAQLQ-TFadministered to a subject having a peanut allergy at a first time pointbefore being informed they are to be administered, or are beingadministered, a peanut composition according to an oral immunotherapyschedule is 4 or higher. In some embodiments, the score of one or moredomains of a FAQLQ-TF administered to a subject having a peanut allergyat a first time point before being informed they are to be administered,or are being administered, a peanut composition according to an oralimmunotherapy schedule is 4 or higher, such as a score of 4 or higher inthe Allergen Avoidance and Dietary Restrictions domain, a score of 4 orhigher in the Emotional Impact domain, and/or a score of 4 or higher inthe Risk of Accidental Exposure domain. In some embodiments, the totalscore of a FAQLQ-TF administered to a subject with a peanut allergy at asecond time point after a period after being informed they are to beadministered, or are being administered, a peanut composition accordingto an oral immunotherapy schedule as compared to the total score of aFAQLQ-TF administered to said subject at a first time point before beinginformed is improved by at least 0.5 points, such as at least 1 point,at least 2 points, at least 3 points, or at least 4 points. In someembodiments, the score of a domain of a FAQLQ-TF administered to asubject having a peanut allergy is improved by at least 0.5 points, suchas at least 0.5 points in the Allergen Avoidance and DietaryRestrictions domain, at least 0.5 points in the Emotional Impact domain,and/or at least 0.5 points in the Risk of Accidental Exposure domain ata second time point after being informed they are to be administered, orare being administered, a peanut composition according to an oralimmunotherapy schedule as compared to the score in each domain at afirst time point before being informed. In some embodiments, the periodof oral immunotherapy between a first time point and a second time pointis at least one month of oral immunotherapy. In some embodiments, theperiod between the first time point and the second time point comprisesan up-dosing phase of the oral immunotherapy. In some embodiments, theperiod of oral immunotherapy between the first time point and the secondpoint comprises at least 1 month of maintenance therapy, such as atleast 2 months, at least 3 months, at least 4 months, at least 5 months,at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a subject having a peanutallergy is determined by one or more QoLQs, wherein at least one QoLQ isa FAQLQ-AF. In some embodiments, the total score of a FAQLQ-AFadministered to a subject having a peanut allergy at a first time pointbefore an oral immunotherapy or during the up-dosing phase of an oralimmunotherapy is 4 or higher. In some embodiments, the score of one ormore domains of a FAQLQ-AF administered to a subject having a peanutallergy at a first time point before an oral immunotherapy or during theup-dosing phase of an oral immunotherapy is 4 or higher, such as a scoreof 4 or higher in the Allergen Avoidance and Dietary Restrictionsdomain, a score of 4 or higher in the Emotional Impact domain, a scoreof 4 or higher in the Food Allergy Related Health domain, and/or a scoreof 4 or higher in the Risk of Accidental Exposure domain. In someembodiments, the total score of a FAQLQ-AF administered to a subjectwith a peanut allergy at a second time point after a period of oralimmunotherapy as compared to the total score of a FAQLQ-AF administeredto said subject at a first time point before the oral immunotherapy isimproved by at least 0.5 points, such as at least 1 point, at least 2points, at least 3 points, or at least 4 points. In some embodiments,the total score of a FAQLQ-AF administered to a subject with a peanutallergy at a second time point after a period of oral immunotherapy ascompared to the total score of a FAQLQ-AF administered to said subjectat a first time point during the up-dosing phase of an oralimmunotherapy is improved by at least 0.5 points, such as at least 1point, at least 2 points, at least 3 points, or at least 4 points. Insome embodiments, the score of a domain of a FAQLQ-AF administered to asubject having a peanut allergy is improved by at least 0.5 points, suchas at least 0.5 points in the Allergen Avoidance and DietaryRestrictions domain, at least 0.5 points in the Emotional Impact domain,at least 0.5 points in the Food Allergy Related Health domain, and/or atleast 0.5 points in the Risk of Accidental Exposure domain at a secondtime point after a period of oral immunotherapy as compared to the scorein each domain at a first time point before the oral immunotherapy orduring the up-dosing phase of the oral immunotherapy. In someembodiments, the subject is informed they are to be administered apeanut composition before the oral immunotherapy. In some embodiments,the period of oral immunotherapy between the first time point and thesecond time point comprises an up-dosing phase of the oralimmunotherapy. In some embodiments, the period of oral immunotherapybetween the first time point and the second point is at least 1 month ofmaintenance therapy, such as at least 2 months, at least 3 months, atleast 4 months, at least 5 months, at least 6 months, or at least 12months of maintenance therapy.

In some embodiments, the quality of life of a subject having a peanutallergy is determined by one or more QoLQs, wherein at least one QoLQ isa FAQLQ-AF. In some embodiments, the total score of a FAQLQ-TFadministered to a subject having a peanut allergy at a first time pointbefore being informed they are to be administered, or are beingadministered, a peanut composition according to an oral immunotherapyschedule is 4 or higher. In some embodiments, the score of one or moredomains of a FAQLQ-AF administered to a subject having a peanut allergyat a first time point before being informed they are to be administered,or are being administered, a peanut composition according to an oralimmunotherapy schedule is 4 or higher, such as a score of 4 or higher inthe Allergen Avoidance and Dietary Restrictions domain, a score of 4 orhigher in the Emotional Impact domain, a score of 4 or higher in theFood Allergy Related Health domain, and/or a score of 4 or higher in theRisk of Accidental Exposure domain. In some embodiments, the total scoreof a FAQLQ-AF administered to a subject with a peanut allergy at asecond time point after a period after being informed they are to beadministered, or are being administered, a peanut composition accordingto an oral immunotherapy schedule as compared to the total score of aFAQLQ-AF administered to said subject at a first time point before beinginformed is improved by at least 0.5 points, such as at least 1 point,at least 2 points, at least 3 points, or at least 4 points. In someembodiments, the score of a domain of a FAQLQ-AF administered to asubject having a peanut allergy is improved by at least 0.5 points, suchas at least 0.5 points in the Allergen Avoidance and DietaryRestrictions domain, at least 0.5 points in the Emotional Impact domain,at least 0.5 points in the Food Allergy Related Health domain, and/or atleast 0.5 points in the Risk of Accidental Exposure domain at a secondtime point after being informed they are to be administered, or arebeing administered, a peanut composition according to an oralimmunotherapy schedule as compared to the score in each domain at afirst time point before being informed. In some embodiments, the periodof oral immunotherapy between the first time point and the second timepoint comprises at least one month of therapy. In some embodiments, theperiod of oral immunotherapy between the first time point and the secondtime point comprises an up-dosing phase of oral immunotherapy. In someembodiments, the period of oral immunotherapy between the first timepoint and the second time point is at least 1 month of maintenancetherapy, such as at least 2 months, at least 3 months, at least 4months, at least 5 months, at least 6 months, or at least 12 months ofmaintenance therapy.

In some embodiments, the quality of life of a subject having a peanutallergy is determined by one or more QoLQs, wherein at least one QoLQ isa proxy-reported FAQLQ-PF administered to a subject's caregiver. In someembodiments, the total score of a FAQLQ-PF administered to a subject'scaregiver at a first time point before an oral immunotherapy or duringthe up-dosing phase of an oral immunotherapy is 4 or higher. In someembodiments, the score of one or more domains of a FAQLQ-PF administeredto a subject's caregiver at a first time point before an oralimmunotherapy or during the up-dosing phase of an oral immunotherapy is4 or higher, such as a score of 4 or higher in the Emotional Impactdomain, a score of 4 or higher in the Food-related Anxiety domain,and/or a score of 4 or higher in the Dietary and Social Restrictionsdomain. In some embodiments, the total score of a FAQLQ-PF administeredto a subject's caregiver at a second time point after a period of oralimmunotherapy as compared to the total score of a FAQLQ-PF administeredto said subject's caregiver at a first time point before the oralimmunotherapy is improved by at least 0.5 points, such as at least 1point, at least 2 points, at least 3 points, or at least 4 points. Insome embodiments, the total score of a FAQLQ-PF administered to asubject's caregiver at a second time point after a period of oralimmunotherapy as compared to the total score of a FAQLQ-PF administeredto said subject's caregiver at a first time point during the up-dosingphase of an oral immunotherapy is improved by at least 0.5 points, suchas at least 1 point, at least 2 points, at least 3 points, or at least 4points. In some embodiments, the score of a domain of a FAQLQ-PFadministered to a subject's caregiver is improved by at least 0.5points, such as at least 0.5 points in the Emotional Impact domain, atleast 0.5 points in the Food-related Anxiety domain, and/or at least 0.5points in the Dietary and Social Restrictions domain at a second timepoint after a period of oral immunotherapy as compared to the score ineach domain at a first time point before the oral immunotherapy orduring the up-dosing phase of the oral immunotherapy. In someembodiments, the subject is informed they are to be administered apeanut composition before the oral immunotherapy. In some embodiments,the period of oral immunotherapy between the first time point and thesecond time point comprises an up-dosing phase of the oralimmunotherapy. In some embodiments, the period of oral immunotherapybetween the first time point and the second time point is at least 1month of maintenance therapy, such as at least 2 months, at least 3months, at least 4 months, at least 5 months, at least 6 months, or atleast 12 months of maintenance therapy.

In some embodiments, the quality of life of a subject having a peanutallergy is determined by one or more QoLQs, wherein at least one QoLQ isa proxy-reported FAQLQ-PF administered to the subject's caregiver. Insome embodiments, the total score of a FAQLQ-PF administered to asubject's caregiver at a first time point before the subject is informedthey are to be administered, or are being administered, a peanutcomposition according to an oral immunotherapy schedule is 4 or higher.In some embodiments, the score of one or more domains of a FAQLQ-PFadministered to a subject's caregiver at a first time point before thesubject is informed they are to be administered, or are beingadministered, a peanut composition according to an oral immunotherapyschedule is 4 or higher, such as a score of 4 or higher in the EmotionalImpact domain, a score of 4 or higher in the Food-related Anxietydomain, and/or a score of 4 or higher in the Dietary and SocialRestrictions domain. In some embodiments, the total score of a FAQLQ-PFadministered to a subject's caregiver at a second time point after aperiod after the subject is informed they are to be administered, or arebeing administered, a peanut composition according to an oralimmunotherapy schedule as compared to the total score of a FAQLQ-PFadministered to said subject's caregiver at a first time point beforethe subject is informed is improved by at least 0.5 points, such as atleast 1 point, at least 2 points, at least 3 points, or at least 4points. In some embodiments, the score of a domain of a FAQLQ-PFadministered to a subject's caregiver is improved by at least 0.5points, such as at least 0.5 points in the Emotional Impact domain, atleast 0.5 points in the Food-related Anxiety domain, and/or at least 0.5points in the Dietary and Social Restrictions domain at a second timepoint after a period after the subject is informed they are to beadministered, or are being administered, a peanut composition accordingto an oral immunotherapy schedule as compared to the score in eachdomain at a first time point before being informed. In some embodiments,the period of oral immunotherapy between the first time point and thesecond time point is at least one month of oral immunotherapy. In someembodiments, the period of oral immunotherapy between the first timepoint and the second time point comprises an up-dosing phase of the oralimmunotherapy. In some embodiments, the period of oral immunotherapybetween the first time point and the second time point comprises atleast 1 month of maintenance therapy, such as at least 2 months, atleast 3 months, at least 4 months, at least 5 months, at least 6 months,or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a subject having a peanutallergy is determined by one or more QoLQs, wherein at least one QoLQ isa FAIM. In some embodiments, the total score of a FAIM administered to asubject having a peanut allergy at a first time point before an oralimmunotherapy or during the up-dosing phase of an oral immunotherapy is4 or higher. In some embodiments, the total score of a FAIM administeredto a subject with a peanut allergy after at a second time point after aperiod of oral immunotherapy as compared to the total score of a FAIMadministered to said subject at a first time point before the oralimmunotherapy is improved by at least 0.5 points, such as at least 1point, at least 2 points, at least 3 points, or at least 4 points. Insome embodiments, the total score of a FAIM administered to a subjectwith a peanut allergy at a second time point after a period of oralimmunotherapy as compared to the total score of a FAIM administered tosaid subject at a first time point during the up-dosing phase of an oralimmunotherapy is improved by at least 0.5 points, such as at least 1point, at least 2 points, at least 3 points, or at least 4 points. Insome embodiments, the subject is informed they are to be administered apeanut composition before the oral immunotherapy. In some embodiments,the period of oral immunotherapy between the first time point and thesecond time point comprises an up-dosing phase. In some embodiments, theperiod of oral immunotherapy between the first time point and the secondtime point comprises at least 1 month of maintenance therapy, such as atleast 2 months, at least 3 months, at least 4 months, at least 5 months,at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a subject having a peanutallergy is determined by one or more QoLQs, wherein at least one QoLQ isa FAIM. In some embodiments, the total score of a FAIM administered to asubject having a peanut allergy at a first time point before beinginformed they are to be administered, or are being administered, apeanut composition according to an oral immunotherapy schedule is 4 orhigher. In some embodiments, the total score of a FAIM administered to asubject with a peanut allergy at a second time point after a periodafter being informed they are to be administered, or are beingadministered, a peanut composition according to an oral immunotherapyschedule as compared to the total score of a FAIM administered to saidsubject at a first time point before being informed is improved by atleast 0.5 points, such as at least 1 point, at least 2 points, at least3 points, or at least 4 points. In some embodiments, the period of oralimmunotherapy between a first time point and a second time point is atleast one month of therapy. In some embodiments, the period between afirst time point and a second time point comprises an up-dosing phase ofthe oral immunotherapy. In some embodiments, the period of oralimmunotherapy between a first time point and a second point is at least1 month of maintenance therapy, such as at least 2 months, at least 3months, at least 4 months, at least 5 months, at least 6 months, or atleast 12 months of maintenance therapy.

Peanut Oral Immunotherapy

In some embodiments, the quality of life of a subject having a peanutallergy can be improved by administering a series of doses of a peanutprotein composition, according to a dosing schedule, to the subjectduring the course of an oral immunotherapy. In some embodiments, thequality of life of a subject having a peanut allergy can be improved byinforming the subject they are to be, or are being, administered aseries of doses of a peanut protein composition, according to a dosingschedule, to the subject during the course of an oral immunotherapy. Insome embodiments, the quality of life of a subject having a peanutallergy can be improved by instructing the subject's caregiver to informthe subject they are to be, or are being, administered a series of dosesof a peanut protein composition, according to a dosing schedule, to thesubject during the course of an oral immunotherapy.

The full length of the oral immunotherapy, for example the duration ofthe up-dosing phase, may vary between subjects depending on the age,health conditions, the nature and type of peanut allergy, concurrentinterventions, and/or complicating indications, among others. Thetherapy is generally multi-phasic, and includes at least an up-dosingphase and a maintenance phase. In some embodiments, the oralimmunotherapies may further include an initial escalation phasepreceding the up-dosing phase. The doses of the peanut proteincomposition administered in the up-dosing and maintenance phases can beperiodically adjusted or scheduled to increase, decrease, or stay thesame. The size of the doses of the peanut protein compositionadministered in the up-dosing and maintenance phases can be adjusted asnecessary based on the judgment of a subject's medical caregiver and/orthe needs of the subject.

Methods of diagnosing peanut allergy are known in the art and includeimmunological assays (such as peanut-specific IgE), skin prick tests,food challenges, and trial elimination diets. For diagnosis of peanutallergy by food challenge, the subject receives increasing doses ofpeanut protein. An observed allergic reaction to the peanut proteinduring the food challenge indicates the subject has a peanut allergy andis a candidate for peanut oral immunotherapy. The judgment of whether asubject reacts to a particular dose during the food challenge depends onthe test criteria, which can vary. A reaction in a food challenge can bejudged by the severity of symptoms (e.g., mild, moderate, or severe)and/or the observability of the symptom (e.g., whether a symptom issubjectively reported by the patient or objectively observed by themedical caregiver).

A subject undergoing peanut OIT as described herein for improving thesubject's quality of life has a known or suspected peanut allergy. Insome embodiments, the subject has previously attempted or completed apeanut protein OIT. In some embodiments, the previous peanut protein OITwas ineffective (for example, by failing to induce acceptabledesensitization, producing unacceptable allergic adverse reactions,failing to impart adequate protection from accidental exposure to peanutprotein, or failing to improve the subject's quality of life), wasterminated by the patient due to discomfort, inconvenience (for example,due to the daily dosing or frequent clinical visits), or necessity (forexample, due to reaction to the peanut protein doses and/or due toallergic adverse events during the course of OIT), or was terminated bythe patient's medical provider (for example, due to allergic adversereaction to peanut protein doses and/or due to allergic adverse eventsduring the course of OIT).

A subject undergoing peanut OIT as described herein for improvement ofthe subject's quality of life may be treatment naïve, having neverundergone a peanut OIT for the improvement of their quality of life. Asubject being diagnosed for peanut allergy by diagnostic exposure topeanut protein, such as in a food challenge, but with no other historyof clinical exposure to peanut protein, is still considered treatmentnaïve after the diagnostic exposure for the purposes of thisapplication.

The subject receiving the oral immunotherapy treatment for improvementof their quality of life is a human subject. In some embodiments, thesubject is about 12 months or older, such as about 12 months to about 48months (for example, about 12 months to about 24 months, about 24 monthsto about 36 months, or about 36 months to about 48 months). In someembodiments, the subject is about 4 years or older. In some embodiments,the subject is between 4 years and less than 18 years old. In someembodiments, the subject is 18 years or older.

The up-dosing phase precedes the maintenance phase, and includesadministration of a series of escalating doses to reach the maximum doseadministered to the subject during the course of oral immunotherapy. Thelength of time of the up-dosing phase can be adapted according the needsof an individual patient, although is generally completed in about 22 toabout 40 weeks. For some patients, the up-dosing phase may last as longas 2 years or more. The up-dosing phase may be extended, for example, ifa patient experiences allergic adverse events after beginning a higherdose in the dosing series.

The up-dosing phase of a peanut OIT typically involves incrementallyincreasing the administered peanut protein dose after a period of time(e.g., approximately every 1-4 weeks). A particular dose in the seriesis repeatedly (e.g., daily) administered to the patient until advancingto the next dose in the series. In some instances, such as when thesubject does not tolerate a particular dose in the series or the subjectexperiences one or more allergic adverse events, the dose is decreasedor the dose in the series is repeated for a period of time prior toadvancing to the next dose in the series. The rate of up-dosing (e.g.,the length of time an individual dose in the series is administered orthe size of the dose increment between doses in the series) may beadjusted based on one or more observed allergic adverse events.

Optionally, the oral immunotherapy includes an initial escalation phasebefore the up-dosing phase, wherein the subject is administered over thecourse of one or two days a series of escalating doses. The initialescalation phase is distinguished from the up-dosing phase by a lowerdose range, shorter intervals between dose escalations, and, typically,closer monitoring by the subject's medical caregiver. For example, a twoday initial escalation may comprise a series of doses from about 0.5 mgto about 6 mg peanut protein, such as individual doses of about 0.5 mg,about 1 mg, about 1.5 mg, about 3 mg, and about 6 mg peanut protein. Thehighest tolerated dose of the initial escalation phase, or a dose lowerthan the highest tolerated dose in the initial escalation phase, may bethe first dose of the up-dosing phase. If a subject does not tolerate atleast a certain dose in the initial escalation phase, the subject may beexcluded from the oral immunotherapy. For example, if a subject suffersa serious allergic adverse event after administration of the 0.5 mg, 1mg, or 1.5 mg peanut protein dose, the subject may not be allowed toproceed to the up-dosing phase. The purposes of the initial escalationphase include calibrating the doses of the up-dosing phase (e.g., theinitial dose of the up-dosing phase), and ensuring the suitability ofthe subject for safely proceeding through an up-dosing phase.

Before, during, or after oral immunotherapy (such as before, during, orafter the up-dosing phase, or before, during, or after the maintenancephase), a subject having a peanut allergy, and/or a subject's caregiver,can undergo a quality of life assessment.

Maintenance Phase Dosing Schedules

The maintenance phase of the peanut oral immunotherapy begins after thehighest dose of the up-dosing phase is achieved. The maintenance phaseis more than about 24 weeks or longer, and may be for the entire life ofthe patient. For example, the length of the maintenance phase may bemore than about 28 weeks, more than about 32 weeks, more than about 36weeks, more than about 40 weeks, more than about 44 weeks, or more thanabout 48 weeks. In some embodiments, the maintenance phase is more thanabout 24 weeks to about 28 weeks, about 28 weeks to about 32 weeks,about 32 weeks to about 36 weeks, about 36 weeks to about 40 weeks,about 40 weeks to about 44 weeks, about 44 weeks to about 48 weeks,about 48 weeks to about 52 weeks, about 52 weeks to about 60 weeks,about 60 weeks to about 72 weeks, about 72 weeks to about 80 weeks, ormore than about 80 weeks, such as the life of the subject. In someembodiments, the maintenance phase is up to about 108 weeks in length.

In some embodiments, the maintenance phase dose is administered to thesubject daily during at least a portion of the maintenance phase. Insome embodiments, the maintenance phase dose is administered to thesubject daily for about 6 months to about 2 years during the maintenancephase, such as about 6 months, about 6 months to about 12 months, about12 months to about 18 months, or about 18 months to about 2 years.

The dosage of peanut protein administered to the subject during themaintenance phase is between about 200 mg and about 1,000 mg peanutprotein. For example, in some embodiments, a dose during the maintenancephase is between about 200 mg and about 300 mg peanut protein, about 300mg and about 500 mg peanut protein, about 500 mg and about 1,000 mgpeanut protein, or values and ranges therebetween. In an exemplaryembodiment, a maintenance phase dose administered to the subject duringthe maintenance phase is about 300 mg peanut protein.

Up-Dosing Phase

The up-dosing phase of an oral immunotherapy comprises administering tothe patient a series of escalating doses, beginning with a lower dosethan the highest dose of the oral immunotherapy and ending with thehighest dose of the oral immunotherapy. Each dose in the series of dosesis administered periodically, such as daily. Each dose in the series cancomprise daily administration of the peanut protein composition for aperiod of time, such as about 1 week to about 4 weeks, such as about 2weeks. After the completion of a particular dose in the series for aperiod of time, treatment can be advanced to a higher dose in theseries. In some embodiments, the up-dosing phase of the treatmentcomprises a series of between 2 and 10 different dose levels. If asubject tolerates a particular dose level during the up-dosing phase fora period of time, the subject can advance to the next dose level in theseries of the up-dosing phase. If a subject does not tolerate aparticular dose level during the up-dosing phase for a period of time,the subject may repeat the current dose level in the series.Alternatively, if a subject does not tolerate a particular dose levelduring the up-dosing phase for a period of time, the subject may returnto an earlier dose level in the series. The duration of the up-dosingphase therefore depends on the specific responses of the subject. Thesubject may repeat doses in the series as many times as necessary toachieve the highest dose in the series. The up-dosing phase ends whenthe highest dose is tolerated for two weeks.

The pharmaceutical composition of peanut protein of a dose administeredduring the up-dosing phase comprises between about 0.5 mg and about5,000 mg of peanut protein, such as about 0.5 mg to about 10 mg peanutprotein, about 10 mg to about 100 mg peanut protein, about 100 mg toabout 300 mg peanut protein, about 300 mg to about 500 mg peanutprotein, about 500 mg to about 1,000 mg peanut protein, about 1,000 mgto about 2,000 mg peanut protein, or about 2,000 mg to about 5,000 mgpeanut protein and values and ranges therebetween. In a non-limitingexemplary embodiment, the doses of the up-dosing phase are dailyadministrations of the maximum tolerated dose of the initial escalationphase, such as 3 mg or 6 mg peanut protein, followed by a series ofdoses of about 12 mg peanut protein, about 20 mg peanut protein, about40 mg peanut protein, about 80 mg peanut protein, about 120 mg peanutprotein, about 160 mg peanut protein, about 200 mg peanut protein, about240 mg peanut protein, and about 300 mg peanut protein, wherein eachdosage level is administered for about 1 week to about 4 weeks (such asabout 2 weeks) before advancing to the next dose in the series. Inanother exemplary embodiment, the doses of the up-dosing phase are dailyadministrations of the maximum tolerated dose of the initial escalationphase, such as 3 mg or 6 mg peanut protein, followed by a series ofescalating daily doses prescribed by a subject's medical caregiver,wherein each daily dose comprises one or more capsules or sachetsselected from the group consisting of: 0.5 mg peanut protein capsules, 1mg peanut protein capsules, 10 mg peanut protein capsules, 20 mg peanutprotein capsules, 100 mg peanut protein capsules, or 300 mg peanutprotein sachets, wherein each dosage level is administered for about 1week to about 4 weeks (such as about 2 weeks) before advancing to thenext dose in the series.

The series of doses of the up-dosing phase are distinguished byadjustment of the administered dose. The size of the dose in the seriesof doses of the up-dosing phase are adjusted periodically, such asbetween once every week and once every six weeks. In some embodiments,the up-dosing phase comprises weekly dose adjustment, dose adjustmentevery two weeks, dose adjustment every third week, dose adjust everyfourth week, dose adjustment every fifth week, dose adjustment everysixth week, or adjustment as needed based on the judgment of thesubject's medical caregiver. The dose may be increased to the nextscheduled dose in the series, lowered to a previous in the series inresponse to an allergic adverse event, maintained for an additionalinterval at the current dose in the series, increased to a higher dosein the series based on the judgment of the subject's medical caregiver,or decreased to a lower dose in the series based on the judgment of thesubject's medical caregiver. In some embodiments, the up-dosing phase isadjusted at any time based on the judgment of the subject's medicalcaregiver that the subject did not tolerate the current dose in theseries.

The up-dosing phase proceeds until the subject achieves the final dosein the up-dosing series. In some embodiments, the up-dosing phase isabout 1 month to about 6 months, such as about 1 month to about 3months, or about 3 months to about 6 months. In some embodiments, theup-dosing phase is about 6 months to about 2 years, such as about 6months to about 1 year, about 1 year to about 18 months, or about 18months to about 2 years. In a non-limiting exemplary embodiment, theup-dosing phase continues for 22 weeks to 2 years, depending on thenumber of dose reductions and re-escalations and dose level repeats,through doses of 12 mg peanut protein, 20 mg peanut protein, 40 mgpeanut protein, 80 mg peanut protein, 120 mg peanut protein, 160 mgpeanut protein, 200 mg peanut protein, 240 mg peanut protein, andterminating at 300 mg peanut protein. In any of the describedembodiments, the up-dosing phase terminates when the subject toleratesthe scheduled dose of the final dose in the series of the up-dosingphase for 2 weeks, thereby beginning the maintenance phase.

Each dose of the series of the up-dosing phase may be scheduled to lastabout 1 week, about 2 weeks, about 3 weeks, about 4 weeks, or values andranges therebetween. Based on the observation of an allergic adverseevent, a subject's caregiver may repeat the subject's current dose inup-dosing series. A particular portion with a particular dose may berepeated as many times as necessary, such as once, two times, threetimes, or four times, or more, to adequately desensitize a subject tothat dose, such as when the subject no longer experiences a moderate orserious allergic adverse event upon accidental (or deliberate) exposureto the food allergen.

Initial Escalation Phase

Optionally, the oral immunotherapy includes an initial escalation phasepreceding the up-dosing phase. The initial escalation phase can ensurethe safety and suitability of oral immunotherapy for a particularsubject. The initial escalation phase is administered over a shortperiod, such as one or two days, at an appropriate medical facility,such as a doctor's office or allergy clinic. The subject is usuallyclosely monitored by a medical caregiver, who can provide interventionssuch as epinephrine, albuterol, and diphenhydramine in the event of anallergic adverse reaction that necessitates intervention. The initialescalation phase of the oral immunotherapy, if present, includesadministration of a plurality of small doses of the peanut proteincomposition to the subject. The small doses can be spaced by a period oftime, such as about 10 minutes to about 60 minutes, and can include 1,2, 3, 4, or 5 or more doses.

The initial escalation phase may comprise doses between about 0.5 mg andabout 6 mg peanut protein, such as about 0.5 mg to about 1.5 mg peanutprotein, about 1.5 mg to about 3 mg peanut protein, or about 3 mg toabout 6 mg peanut protein. In a non-limiting example, the initialescalation phase comprises an incremental escalation over one day fromabout 0.5 mg peanut protein to a maximum of about 6 mg peanut protein ina single day, with single doses of about 0.5 mg, about 1 mg, about 1.5mg, about 3 mg, and about 6 mg of peanut protein, wherein tolerance ofthe 3 mg or 6 mg peanut protein dose indicates the subject can safelyproceed to an up-dosing phase of an oral immunotherapy.

Compositions for Oral Immunotherapy

Exemplary compositions for treating peanut allergy are described indetail in U.S. Publication No. 2014/0271721, the contents of which areincorporated by reference herein in its entirety. Exemplary methods forpreparing peanut protein formulations are described in detail in U.S.Publication No. 2014/0271836, the contents of which are incorporated byreference herein in its entirety.

The quality of life of a subject having a peanut allergy can be improvedby administering a series of doses of a peanut protein composition tothe subject during the course of a peanut protein oral immunotherapy.The peanut protein composition is preferably a pharmaceuticalcomposition comprising one or more peanut allergen proteins for treatingpeanut allergy. In some embodiments, peanut proteins may be isolatedfrom peanut flour and, optionally, further comprise one or morediluents, one or more glidants, and one or more lubricants. In someembodiments, the pharmaceutical composition of peanut protein comprisesbetween about 0.05% to about 100% w/w of peanut protein.

In some embodiments, the pharmaceutical composition of peanut proteincomprises characterized peanut protein. In some embodiments thecharacterized peanut protein comprises characterized peanut allergenproteins Ara h1, Ara h2, and/or Ara h6. In one embodiment, a finalformulation for treating peanut allergy comprises peanut flour,comprising characterized peanut allergen proteins Ara h1, Ara h2, and/orAra h6, formulated with a diluent, a glidant, and a lubricant ingraduated doses comprising capsules containing between about 0.5 andabout 5,000 mg of peanut protein for administration in up-dosing,maintenance, and/or initial escalation phases of an oral immunotherapy.

In any of the methods described herein, the pharmaceutical compositionof peanut protein for administration in a maintenance phase of an oralimmunotherapy may comprise a dose of between about 200 mg to about 1,000mg peanut protein, such as between about 200 mg and about 250 mg peanutprotein, about 250 mg and about 300 mg peanut protein, about 300 mg andabout 500 mg peanut protein, and about 500 mg and about 1,000 mg peanutprotein. In a non-limiting preferred embodiment, the dose of peanutprotein for administration in the maintenance phase of an oralimmunotherapy is about 300 mg peanut protein.

In some embodiments, the pharmaceutical composition of peanut proteinfor administration in an up-dosing phase of an oral immunotherapycomprises between about 0.5 mg and about 5,000 mg peanut protein, suchas individual doses in a series of about 3 mg, about 6 mg, about 10 mg,about 12 mg, about 20 mg, about 40 mg, about 80 mg, about 100 mg, about120 mg, about 160 mg, about 200 mg, about 240 mg, and about 300 mgpeanut protein. In a non-limiting exemplary embodiment, the doses ofpeanut protein for administration in an up-dosing phase of an oralimmunotherapy are daily administration of the maximum tolerated dose ofthe initial escalation phase, such as about 3 mg peanut protein or about6 mg peanut protein, followed by a series of escalating daily dosesprescribed by a subject's medical caregiver, wherein each daily dosecomprises one or more capsules or sachets selected from the groupconsisting of: about 0.5 mg peanut protein capsules, about 1 mg peanutprotein capsules, about 10 mg peanut protein capsules, about 20 mgpeanut protein capsules, about 100 mg peanut protein capsules, or about300 mg peanut protein sachets, wherein each dosage level is administeredfor about 1 week to about 4 weeks (such as about 2 weeks) beforeadvancing to the next dose.

In the methods described herein, an oral immunotherapy may optionallycomprise an initial escalation phase. In some embodiments, thepharmaceutical composition of peanut protein for administration in aninitial escalation phase of an oral immunotherapy comprises betweenabout 0.5 and about 6 mg of peanut protein, such as individual doses ofabout 0.5 mg, about 1 mg, about 1.5 mg, about 3 mg, and about 6 mgpeanut protein. In some embodiments, the pharmaceutical composition ofpeanut protein for administration in an initial escalation phase of anoral immunotherapy comprises between about 0.5 and about 6 mg of peanutprotein, such as individual doses of about 0.5 mg, about 1 mg, about 1.5mg, about 3 mg, about 6 mg, and about 12 mg peanut protein.

EXEMPLARY EMBODIMENTS

The invention may be better understood by reference to the followingexemplary embodiments. However, the exemplary embodiments are notintended to limit the scope of the invention described herein.

Embodiment 1. A method of improving the quality of life of a patientwith a peanut allergy, comprising: administering to the patient a peanutcomposition according to an oral immunotherapy schedule.

Embodiment 2. The method of embodiment 1, wherein the patient isinformed that the peanut composition is being administered.

Embodiment 3. The method of embodiment 2, wherein the patient isinformed that the peanut composition is being administered to thepatient at the start of the oral immunotherapy schedule.

Embodiment 4. The method of embodiment 2, wherein the patient isinformed that the peanut composition is being administered to thepatient during an up-dosing phase of the oral immunotherapy schedule.

Embodiment 5. The method of embodiment 2, wherein the patient isinformed that the peanut composition is being administered to thepatient during a maintenance phase of the oral immunotherapy schedule.

Embodiment 6. The method of embodiment 1, further comprising informingthe patient that the peanut composition is being administered to thepatient.

Embodiment 7. The method of embodiment 6, wherein the patient isinformed that the peanut composition is being administered to thepatient prior to the start of the oral immunotherapy schedule.

Embodiment 8. The method of embodiment 6, wherein the patient isinformed that the peanut composition is being administered to thepatient during an up-dosing phase of an oral immunotherapy schedule.

Embodiment 9. The method of embodiment 6, wherein the patient isinformed that the peanut composition is being administered to thepatient during a maintenance phase of the oral immunotherapy schedule.

Embodiment 10. The method of any one of embodiments 1-9, wherein thequality of life improvement is measured using a quality of lifequestionnaire (QoLQ).

Embodiment 11. The method of embodiment 10, wherein the QoLQ comprisesone or more scored domains of measurement.

Embodiment 12. The method of embodiment 11, wherein the QoLQ is a FoodAllergy Quality of Life Questionnaire (FAQLQ).

Embodiment 13. The method of embodiment 12, wherein the FAQLQ is aFAQLQ-child form (FAQLQ-CF), FAQLQ-teen form (FAQLQ-TF), FAQLQ-adultform (FAQLQ-AF), or FAQLQ-parent form (FAQLQ-PF).

Embodiment 14. The method of embodiment 10, wherein the QoLQ is a FoodAllergy Independent Measure (FAIM).

Embodiment 15. The method of embodiment 14, wherein the FAIM is aFAIM-child form (FAIM-CF), FAIM-teen form (FAIM-TF), FAIM-adult form(FAIM-AF), or FAIM-parent form (FAIM-PF).

Embodiment 16. A method of improving the quality of life of a patientwith a peanut allergy, as assessed by a quality of life questionnaire(QoLQ), the method comprising administering to the patient a peanutcomposition according to an oral immunotherapy schedule.

Embodiment 17. The method of embodiment 16, wherein the patient isinformed that the peanut composition is being administered.

Embodiment 18. The method of embodiment 17, wherein the patient isinformed that the peanut composition is being administered to thepatient at the start of the oral immunotherapy schedule.

Embodiment 19. The method of embodiment 17, wherein the patient isinformed that the peanut composition is being administered to thepatient during an up-dosing phase of the oral immunotherapy schedule.

Embodiment 20. The method of embodiment 17, wherein the patient isinformed that the peanut composition is being administered to thepatient during a maintenance phase of the oral immunotherapy schedule.

Embodiment 21. The method of embodiment 16, further comprising informingthe patient that the peanut composition is being administered to thepatient.

Embodiment 22. The method of embodiment 21, wherein the patient isinformed that the peanut composition is being administered to thepatient prior to the start of the oral immunotherapy schedule.

Embodiment 23. The method of embodiment 21, wherein the patient isinformed that the peanut composition is being administered to thepatient during an up-dosing phase of an oral immunotherapy schedule.

Embodiment 24. The method of embodiment 21, wherein the patient isinformed that the peanut composition is being administered to thepatient during a maintenance phase of the oral immunotherapy schedule.

Embodiment 25. The method of any one of embodiments 16-24, wherein theQoLQ comprises one or more scored domains of measurement.

Embodiment 26. The method of embodiment 25, wherein the QoLQ is a FoodAllergy Quality of Life Questionnaire (FAQLQ).

Embodiment 27. The method of embodiment 26, wherein the FAQLQ is aFAQLQ-child form (FAQLQ-CF), FAQLQ-teen form (FAQLQ-TF), FAQLQ-adultform (FAQLQ-AF), or FAQLQ-parent form (FAQLQ-PF).

Embodiment 28. The method of embodiment 25, wherein the QoLQ is a FoodAllergy Independent Measure (FAIM).

Embodiment 29. The method of embodiment 28, wherein the FAIM is aFAIM-child form (FAIM-CF), FAIM-teen form (FAIM-TF), FAIM-adult form(FAIM-AF), or FAIM-parent form (FAIM-PF).

Embodiment 30. The method of embodiment 25, wherein the QoLQ is aPediatric Quality of Life Inventory (PedsQL).

Embodiment 31. The method of any one of embodiments 1-30, wherein thequality of life is improved for at least 6 months.

Embodiment 32. The method of any one of embodiments 1-31, wherein thequality of life is improved for at least 12 months.

Embodiment 33. The method of any one of embodiments 11-13 or 25-27,wherein the one or more scored domains of the QoLQ are each scored on ascale between 1 and 7, or are each converted to a score between a firstscore and a second score, wherein the second score indicates worsequality of life.

Embodiment 34. The method of any one of embodiments 11-13 or 25-27,wherein an improvement in the patient's quality of life is at least 0.5points in one or more domains of the QoLQ at a second time point after aperiod of oral immunotherapy as compared to an assessment at a firsttime point before the period of oral immunotherapy.

Embodiment 35. The method of any one of embodiments 11-17 or 25-34,wherein an improvement in the patient's quality of life is at least 0.5points in a total score of the QoLQ at a second time point after aperiod of oral immunotherapy as compared to an assessment at a firsttime point before the period of oral immunotherapy; wherein the totalscore is the average of each domain score.

Embodiment 36. The method of embodiment 34 or embodiment 35, wherein theperiod of oral immunotherapy between the first time point and the secondtime point is the up-dosing phase of the oral immunotherapy schedule.

Embodiment 37. The method of embodiment 34 or embodiment 35, wherein theperiod of oral immunotherapy between the first time point and the secondtime point is at least 1 month of a maintenance therapy of the oralimmunotherapy schedule.

Embodiment 38. The method of any one of embodiments 1-37, wherein thequality of life improves after 6 months of the oral immunotherapyschedule.

Embodiment 39. The method of any one of embodiments 1-38, wherein theoral immunotherapy schedule comprises an up-dosing phase and amaintenance phase.

Embodiment 40. The method of embodiment 39, wherein the peanutcomposition is administered to the patient during the maintenance phaseon a daily basis.

Embodiment 41. The method of embodiment 39 or embodiment 40, wherein themaintenance phase is at least 3 months.

Embodiment 42. The method of any one of embodiments 39-41, wherein thepeanut composition is administered to the patient during a maintenancephase of the oral immunotherapy schedule at a dose of about 300 mgpeanut protein or more.

Embodiment 43. The method of any one of embodiments 39-42, wherein theup-dosing phase comprises administering to the patient two or moredifferent doses between about 3 mg and about the dose of an initialmaintenance phase dose.

Embodiment 44. The method of any one of embodiments 1-43, wherein theoral immunotherapy schedule comprises an up-dosing phase that is betweenabout 3 months and about 2 years in length.

Embodiment 45. The method of any one of embodiments 1-44, wherein theoral immunotherapy schedule further comprises an initial escalationphase.

Embodiment 46. The method of any one of embodiments 1-45, wherein thepatient is about 4 years old or older.

Embodiment 47. The method of any one of embodiments 1-46, wherein thepatient is between about 4 years old and about 17 years old.

Embodiment 48. The method of any one of embodiments 1-47, wherein thepatient is between about 8 years old and about 17 years old.

Embodiment 49. The method of any one of embodiments 1-48, wherein themethod comprises measuring the quality of life before administering tothe patient a peanut composition according to an oral immunotherapyschedule.

Embodiment 50. The method of any one of embodiments 1-49, wherein themethod comprises measuring the quality of life after administering tothe patient a peanut composition according to an oral immunotherapyschedule.

Embodiment 51. The method of any one of embodiments 2-15 or 17-50,wherein the method comprises measuring the quality of life afterinforming the patient that the peanut composition is being administered.

Embodiment 52. The method of any one of embodiments 1-51, wherein thequality of life of the patient is improved as determined by a quality oflife questionnaire (QoLQ).

EXAMPLES

The application may be better understood by reference to the followingnon-limiting examples, which are provided as exemplary embodiments ofthe application. The following examples are presented in order to morefully illustrate embodiments and should in no way be construed, however,as limiting the broad scope of the application. While certainembodiments of the present application have been shown and describedherein, it will be obvious that such embodiments are provided by way ofexample only. Numerous variations, changes, and substitutions may occurto those skilled in the art without departing from the spirit and scopeof the invention. It should be understood that various alternatives tothe embodiments described herein may be employed in practicing themethods described herein.

Example 1—Impact of Peanut Allergy on Quality of Life

A study was undertaken to assess the real-world burden of peanut allergyon patients and caregivers in the United States.

In one portion of the study, adolescents 13-17-years-old and caregiversof adolescents 13-17-years-old with self-reported, provider-diagnosedpeanut allergy completed a validated, age-appropriate Food AllergyQuality of Life Questionnaire (FAQLQ-TF for self-report or a FAQLQ-PFfor proxy-report; wherein for each answer 1=no issue and 7=extremeissue). Between-group analyses were conducted (chi square; t-tests). Theadolescents (n=102) and the caregivers for adolescents (n=94) completedthe survey. Key demographic and disease history variables amongadolescents (self-report versus proxy-report) were similar. Adolescentsreported significantly greater burden, versus caregivers, regardinglimitations that living with peanut allergy placed on their day-to-daylife and fear of a reaction impacting emotional well-being, and greatercare in avoiding direct contact with peanuts. Adolescents had higherscores (i.e., poorer quality of life) on the FAQLQ Emotional scalecompared with caregiver assessment (mean 5.07 versus 4.21, p<0.001).Adolescents and caregivers also differed significantly on the mostconcerning aspects of PA, with adolescents expressing more concernregarding physical symptoms during a reaction and the impact of peanutallergy on the family, compared with caregivers of adolescents. Intotal, adolescents reported poorer quality of life (impact on day-to-daylife, emotional well-being, and FAQLQ emotional scale), greater concernregarding physical symptoms of reaction and impact on family, andgreater care in avoiding exposure to peanuts than did caregivers.

Of the self-reported adolescents who completed the FAQLQ-TF, a number ofvariables were statistically significant correlates of FAQLQ-TF Totalscore: psychosocial variables, including impact of fear of a reaction onemotional well-being (p<0.001), daily life limitations (p<0.001), worryregarding epinephrine autoinjector access (p<0.001), confidence managinga reaction (p=0.025), total number of uses of advanced interventions(ER, hospital, IV epinephrine, or intubation) in their lifetime(p=0.003), and severity of their most severe reaction (p=0.006). Therewere no statistically significant correlations with age, sex, number ofother food allergies, and other health conditions, time since mostrecent reaction and since the most severe reaction, the lifetime numberof moderate/severe reactions, and the number of reactions in the lastyear. These data suggest that psychosocial variables and the need tomodify daily activities to practice avoidance, and a history of needingto seek advanced treatment due to exposure, are associated with adecreased disease-specific quality of life.

In another portion of the study, adolescents 13-17-years-old withself-reported, provider-diagnosed peanut allergy completed the PediatricQuality of Life Inventory (PedsQL; scores 0-100, higher is betterquality of life). Between-group analyses were conducted (chi square;t-test). The adolescents with peanut allergy (n=102) had a mean PedsQLTotal score of 48.8. Mean subscale scores were: Physical (53.6),Emotional (43.0), Social (48.2), School (46.0), and Psychosocial (44.5).These scores were significantly below the scale scores from a generalpopulation of 8-16-year-olds (n>5900; range 78.2-87.0) and exceeded theminimum clinically important difference (4.36-9.12 points). Adolescentsexperienced ≥1 peanut allergy-related reaction in the past year hadsignificantly lower PedsQL Total score (p=0.008), as did those receivingclinician intervention for ≥1 peanut allergy reaction in the past year(p<0.001, those “not at all” to “somewhat satisfied” with currentapproaches to peanut allergy reaction prevention (p=0.012), those sayingpeanut allergy limited their day-to-day life “somewhat” to “completely”(p=0.013), or who reported a “great” to “100% chance” of not effectivelydealing with a reaction. Thus, adolescents with peanut allergy havesubstantially lower PedsQL scores than the general population ofsimilarly aged individuals. PedsQL Total scores were significantlydifferent between subgroups defined by recent allergic reaction/need forclinician intervention, satisfaction with reaction prevention, perceivedlimitations on day-to-day life, and concern about their ability to dealwith a reaction.

Example 2—Peanut Oral Immunotherapy Clinical Trials

A) Double-blind clinical trial. A randomized, double-blind,placebo-controlled Phase 3 clinical trial (PALISADE) was conducted withpeanut-allergic subjects aged 4 to 49 years old. Subjects underwent aninitial escalation, followed by an up-dosing phase to a target dose of300 mg per day of peanut protein, followed by an approximately six-monthmaintenance phase comprising administration of 300 mg per day of peanutprotein. See Jones et al., Efficacy and Safety of AR101 in PeanutAllergy: Results from a Phase 3, Randomized, Double-Blind,Placebo-Controlled Trial (PALISADE), J. Allergy Clin. Immunol. 141(2),suppl. AB400 (2018); and Vickery et al., AR101 Oral Immunotherapy forPeanut Allergy, New England J. Medicine, vol. 379, no. 21, pp. 1991-2001(2018).

At baseline screening and at exit of PALISADE, subjects (self-report)and their parents or guardians/caregivers (proxy-report) completed anage-appropriate Food Allergy Quality of Life Questionnaire (FAQLQ; e.g.,FAQLQ-CF, FAQLQ-TF, or FAQLQ-PF). Domain and total scores for subjectsaged ≥8 and parents/caregivers of subjects 4-17-years-old werecalculated. To report results across the clinical trial, self-reportFAQLQ scores were combined into a single child, teen, and adult form(termed FAQLQ-CTAF) using common items (i.e., questions). The scalerange was 1-6 or 1-7, with a higher score indicating a worse QoL.Relationships to demographic and disease history variables were alsoevaluated. 367 peanut-allergic subjects and 442 parents/caregiverscompleted baseline assessments. Results indicated peanut allergy had asignificant impact on subject quality of life. For self-reporting,Emotional Impact had the highest score (4.80), followed by AllergenAvoidance and Dietary Restrictions (4.40), and Risk of AccidentalExposure (4.20). For parents/caregivers, Food Anxiety had the highestscore (4.23), followed by Social and Dietary Limitations (4.17) andEmotional Impact (3.82). See Wang et al., Impact of Peanut Allergy onQuality of Life: Baseline Results from PALISADE, a Phase 3,Double-Blind, Placebo-Controlled Trial for AR101 Oral Immunotherapy, J.Allergy Clin. Immunol. 143(2) (2019).

At baseline screening and at exit of PALISADE, subjects (self-report)and their parents or guardians (proxy-report) also completed anage-appropriate Food Allergy Independent Measure (FAIM; e.g., FAIM-CF orFAIM-PF). The FAIM questionnaires consist of expectation-of-outcome anddisease severity questions. Each FAIM question was scored from 1 to 7,with a higher score indicating a worse QoL (e.g., greatest severityperception or worse expectation of outcome).

B) Open label extension. Some PALISADE completers that were treated withan active formulation (i.e., non-placebo) elected to participate in anopen-label extension (OLE) follow-on clinical trial, wherein the subjectwas informed that they would continue receiving active treatment. Priorto beginning the OLE (at PALISADE exit), subjects (self-report) and/ortheir parents or caregivers/guardians (proxy-report) completed anage-appropriate FAQLQ (e.g., FAQLQ-CF, FAQLQ-TF, or FAQLQ-PF) or FAIM(e.g., FAIM-CF or FAIM-PF). As above, to report results across thetrial, self-reported FAQLQ scores were combined using common items.Subjects participating in the OLE received approximately 6 additionalmonths (i.e., approximately 28 weeks) of maintenance therapy comprisingdaily administrations of 300 mg of peanut protein. At the end of theapproximately 6 additional months of OLE maintenance therapy (i.e.,after approximately 52 weeks total of 300 mg daily peanut proteinmaintenance therapy), subjects received an exit double-blindplacebo-controlled food challenge (DBPCFC). Subjects and/or theirparents/caregivers completed an exit age-appropriate FAQLQ (e.g.,FAQLQ-CF, FAQLQ-TF, or FAQLQ-PF) and FAIM (e.g., FAIM-CF or FAIM-PF).

C) Results. 110 peanut-allergic subjects entered the OLE and 103completed the additional 6 months of daily maintenance therapy. Of thoseenrolling in the OLE trial, 62.7% were between 4 and 11 years old, andthe remaining 37.2% were between 12 and 17 years old.

Among the 68 patients between 8 and 17-years-old who completed the FAQLQself-assessment at the end of the OLE, statistically significantimprovements above the developer-reported minimum clinically importantdifference (MCID) were seen on all individual scales (Allergy Avoidanceand Dietary Restrictions, Risk of Accidental Exposure, and EmotionalImpact) and the Total Score (all p<0.01) compared to the FAQLQ PALISADEbaseline assessments, as reported in FIG. 1 . Among the 72 patientsbetween 8 and 17-years-old who completed the FAIM self-assessment at theend of the OLE, statistically significant improvements above thedeveloper-reported MCID were seen on the Expectation of Outcomesquestions and the total score. Decreases below the MCID were observedfor the questions of Product Avoidance and Social Impact. Subjectsreported improvements in QoL both from PALISADE screening to PALISADEexit (a blinded period) and from PALISADE exit to the OLE exit (anopen-label period). For the FAQLQ self-reports, these changes were ofsimilar magnitude.

As reported in FIG. 2 , statistically significant improvements were alsoobserved for two of the three domains of the FAQLQ-PF completed byparents/guardians regarding 93 peanut-allergic subjects participating inthe OLE (Social and Dietary Limitations: p<0.01; Food Anxiety: p<0.05;Emotional Impact: p=0.07) and the Total Score was also significant(p<0.01) compared to baseline FAQLQ-PF baseline assessments. None of theproxy-reported FAQLQ scores exceeded the threshold indicating a MID asreported by the developer, however. For the FAIM questionnaire, theChild Expectation of Outcomes (by proxy) was only collected fromparents/caregivers of children below 13-years-old. Of these 62parents/caregivers of peanut-allergic children who completed the OLE, astatistically significant decrease in the Child Expectation of Outcomes(by proxy) domain was observed, although the decrease did not exceed thedeveloper-reported MCID. Of the 91 parents/caregivers of peanut-allergicchildren who completed the OLE, the Parent/Caregiver Expectation ofOutcomes domain indicated a statistically significant reduction indomain score at the end of the OLE. This decrease exceeded thedeveloper-reported MID. In contrast to the self-reported QoL measures,the majority of the improvement in QoL as reported by proxy was afterthe peanut-allergic subjects had been informed they were receiving thepeanut protein composition, i.e., after the open label period.

These FAQLQ and FAIM data were also analyzed by variable of foodchallenge outcome, adverse events, and adrenaline use. As indicated inFIG. 3 , subjects who completed the OLE were divided based on toleratingthe 600 mg peanut protein dose in the OLE exit double-blindplacebo-controlled food challenge, on the occurrence of a systemicallergic reaction during either of PALISADE or the OLE clinical trial,and the use of adrenaline during either of PALISADE or the OLE clinicaltrial. In FIG. 3 , the proxy-report for FAIM is limited to ChildExpectation of Outcomes score for subjects aged 4-12-years-old. Peanutprotein OIT was consistently correlated with improvement inself-assessed QoL. The efficacy of the OIT (as measured by the oral foodchallenge, the presence of systemic allergic reactions, and the use ofadrenaline) was associated with reduced improvement, but still improvedas compared to baseline. Surprisingly, improvements in proxy-reportedQoL were consistently less substantial than the self-assessments,suggesting parents/caregivers underestimated the improvement in theirchildren's QoL. The difference in proxy-reported QoL byparents/caregivers of children who did not tolerate the 600 mg peanutprotein dose in the oral food challenge as compared to children who didtolerate the 600 mg peanut protein dose was also more pronounced thanthe self-assessments.

D) Additional treatment cohort. In addition to the cohort of patientsdescribed above (termed “cohort 1” of the open label extension), anothercohort of patients entered the open label extension (termed “cohort3a”). Subjects in cohort 3a, like cohort 1 subjects, were PALISADEcompleters that had been treated with an active formulation (i.e.,non-placebo) and elected to participate in the open-label extensionfollow-on clinical trial, wherein they were informed that they wouldcontinue receiving active treatment. Prior to beginning the OLE (atPALISADE exit), cohort 3a subjects (self-report) and/or their parents orcaregivers/guardians (proxy-report) completed an age-appropriate FAQLQor FAIM, as with the cohort 1 subjects described above. Subjects incohort 3a received approximately 56 additional weeks of maintenancetherapy comprising daily administrations of 300 mg of peanut protein. Atthe end of the approximately 56 additional weeks of maintenance therapy(i.e., after approximately 82 weeks total of 300 mg daily peanut proteinmaintenance therapy), subjects received an exit double-blindplacebo-controlled food challenge. Cohort 3a subjects and/or theirparents/caregivers completed an exit age-appropriate FAQLQ and FAIM.

31 subjects were assigned to cohort 3a, of which 16 completed the exitFAQLQ and 17 completed the exit FAIM assessment. As in cohort 1, cohort3a subject's FAQLQ scores exceeded the developer-reported MID of −0.5for Total scores (mean change −0.63, range −1.36, 0.11). In cohort 1,all subdomains exceeded the MID, whereas in cohort 3a only EmotionalImpact improved beyond the MID. For both cohorts, FAIM Total scoresexceeded the MID (for cohort 1, n=72, mean change −0.60, range −0.83 to−0.36; for cohort 3a, n=17, mean change −0.83, range −1.39 to −0.37).For the FAIM, only subject Expectation of Outcome score exceeded theMID, whereas for cohort 3a subjects all subdomain FAIM scores improvedbeyond the MID. These results indicate that the overall improvement inquality of life after subjects are informed they are on active therapyis maintained over a longer maintenance therapy.

Together, these results suggest peanut OIT may substantially improvepatient-reported QoL across domains of measurement. These improvementsmay exceed patient's parent/caregiver expectations. Improvementsoccurred between initial screening and the initial exit measurement,where the initial exit measures were taken immediately after unblindingof the first trial and after initial desensitization and a maintenanceperiod. However, even though significant desensitization was achievedduring the blinded trial, quality of life improvements continued tomanifest during the unblinded open-label extension trial, leading toeven more substantial improvements across the population.

Example 3—European Peanut Oral Immunotherapy Clinical Trial

A) Trial design. A European phase 3 trial (ARTEMIS) was conducted withpeanut-allergic children who experienced dose-limiting symptoms at ≤300mg peanut protein (˜1 peanut kernel) during an entry double-blindplacebo-controlled food challenge (DBPCFC). The trial was a randomized,placebo-controlled, multicenter trial conducted at 18 sites in sevenEuropean countries: Ireland, France, Germany, Italy, Spain, Sweden, andthe United Kingdom.

Children aged 4-17 years were eligible for enrollment if they had aclinical history of peanut allergy, had a mean peanut skin prick test(SPT) wheal diameter ≥3 mm compared to negative control and/or a serumpeanut-specific immunoglobulin E (psIgE) level ≥0.35 kUA/L (asdetermined by ImmunoCAP®) and experienced dose-limiting symptoms at ≤300mg peanut protein during an entry DBPCFC. Major exclusion criteriaincluded any severe or life-threatening episode of anaphylaxis within 60days of the screening DBPCFC, severe or uncontrolled asthma, a historyof eosinophilic esophagitis, or chronic, recurrent, or severegastrointestinal (GI) symptoms of undiagnosed etiology.

Eligible subjects were randomized in a 3:1 ratio to active (AR101;investigational biologic drug comprising peanut protein) or placebo in aone-day initial dose-escalation phase, where they received sequentiallyadministered doses from 0.5 mg to 6 mg under supervision at the trialsite. During the 20- to 40-week up dosing phase, subjects received adaily dose of peanut protein (AR101) or placebo. Doses were increasedbiweekly until a 300 mg dose was reached and maintained for 3 months (3mg initial to 300 mg final). During the maintenance phase, subjectsreceived a daily dose at home of 300 mg peanut protein for 12 weeks. Anexit DBPCFC was performed at the end-of-trial visit with additional 600mg and 1,000 mg peanut protein challenge doses, as tolerated. Theprimary endpoint was the proportion of participants who could consume asingle dose of 1,000 mg peanut protein (˜3-4 peanut kernels) withoutdose-limiting symptoms at exist DBPCFC. Additional endpoints includedadverse event (AE) frequency and severity, and changes in foodallergy-related quality of life (QoL).

QoL was assessed using the FAQLQ and FAIM measures. Age-appropriateversions of FAQLQ and FAIM were completed by participants aged 8-12 and13-17 years of age, and all caregivers at two time points during thetrial: before the screening DBPCFC and at the end-of-trial visit,immediately after the exit DBPCFC and unblinding. Both instrumentsutilized a seven-point scale where one indicates minimal impairment,seven indicates maximal impairment and a change of ≥0.5 is considered tohave exceeded the developer-referenced minimal important difference(MID).

B) Results. All primary and secondary endpoints were met. 77 of the 132(58.3%) actively treated participants tolerated a 1,000 mg peanutprotein exit challenge dose compared with 1 (2.3%) on placebo (treatmentdifference: 56.0%; 95% CI: 44.1, 65.2; p<0.0001).

Significant improvements in self-reported and caregiver proxy-reportedquality of life assessments were found in participants who receivedAR101. Improved QoL was self-reported in participants aged 8-12 in theactive group across all FAQLQ domains. Improvements were statisticallysignificant for the total score and for the “Allergen avoidance anddietary restrictions” and “Risk of accidental exposure” domains (LS meandifference active-placebo [95% CI]: −1.09 [−1.95, −0.22]; −1.18 [−2.06,−0.30]; −1.20 [−2.26, −0.15]; respectively; p<0.05 for all).

Improvements in self-reported and proxy-reported QoL were observed tovarying degrees across all FAIM domains. Compared to the placebo group,improved scores that exceeded MID for the domains “likelihood of asevere reaction” and “chance of dying from accidental allergen exposure”were self- and proxy-reported by participants and caregivers in theactive group, respectively. Improved scores were proxy- andself-reported by caregivers for the domain “effectively treat/be treatedupon accidental exposure” (LS mean treatment different active-placebo[95% CI] caregivers 4-12 years self-report: 0.85 [−0.17, 1.88] p>0.05;caregivers 4-12 years proxy-report: 0.67 [−0.43, 1.77] p>0.05;caregivers 13-17 years self-report: 0.98 [0.03, 1.94] p=0.04). The FAQLQand FAIM results are summarized in FIGS. 4-6 .

Due to exposure to allergenic material, active participants, asexpected, experienced increased treatment-related adverse eventscompared with the placebo group, which might reduce quality of life.Against this expectation, no worsening of QoL that reached the MID wasobserved in any FAQLQ or FAIM domains in the active group compared withthe placebo group.

1-52. (canceled)
 53. A method comprising administering a peanutcomposition to a patient according to an oral immunotherapy schedulecomprising an up-dosing phase and a maintenance phase, the oralimmunotherapy schedule improves a total Food Allergy Independent Measure(FAIM) score of the patient from a first time to a second time by atleast 0.5 points, wherein the first time is selected from the groupconsisting of (i) before the oral immunotherapy schedule and (ii) duringthe up-dosing phase of the oral immunotherapy schedule, wherein a timeperiod that is between the first time and the second time comprises atleast one of (a) the up-dosing phase of the oral immunotherapy scheduleor (b) at least one month of the maintenance phase of the oralimmunotherapy schedule.
 54. The method of claim 53, wherein the peanutcomposition is administered to the patient on a daily basis during atleast the maintenance phase of the oral immunotherapy schedule.
 55. Themethod of claim 53, wherein the maintenance phase of the oralimmunotherapy schedule is at least 3 months.
 56. The method of claim 53,wherein the peanut composition is administered to the patient during amaintenance phase of the oral immunotherapy schedule at a dose betweenabout 200 mg and about 300 mg of peanut protein.
 57. The method of claim53, wherein the up-dosing phase comprises administering to the patienttwo or more different doses between about 3 mg of peanut protein andabout an amount of an initial dose of peanut protein of the maintenancephase.
 58. The method of claim 53, wherein the up-dosing phase has aduration between about 3 months and about 2 years.
 59. The method ofclaim 53, wherein the patient has an age between about 4 years and about17 years.
 60. The method of claim 53, further comprising informing thepatient that the peanut composition is being administered to thepatient.
 61. The method of claim 60, wherein the informing is at one ormore of: prior to the start of the oral immunotherapy schedule, at thestart of the oral immunotherapy schedule, during the up-dosing phase ofan oral immunotherapy schedule, or during the maintenance phase of theoral immunotherapy schedule.
 62. The method of claim 53, wherein theoral immunotherapy schedule improves the total FAIM score of the patientby at least 1 point at the second time relative to the first time. 63.The method of claim 53, wherein the oral immunotherapy schedule improvesthe total FAIM score of the patient by at least 2 points at the secondtime relative to the first time.
 64. The method of claim 53, wherein theoral immunotherapy schedule improves the total FAIM score of the patientby at least 3 points at the second time relative to the first time. 65.The method of claim 53, wherein the oral immunotherapy schedule improvesthe total FAIM score of the patient by at least 4 points at the secondtime relative to the first time.
 66. The method of claim 53, wherein thetime period of the oral immunotherapy schedule that is between the firsttime and the second time comprises at least 2 months of the maintenancephase of the oral immunotherapy schedule.
 67. The method of claim 53,wherein the time period of the oral immunotherapy schedule that isbetween the first time and the second time comprises at least 3 monthsof the maintenance phase of the oral immunotherapy schedule.
 68. Themethod of claim 53, wherein the time period of the oral immunotherapyschedule that is between the first time and the second time comprises atleast 4 months of the maintenance phase of the oral immunotherapyschedule.
 69. The method of claim 53, wherein the time period of theoral immunotherapy schedule that is between the first time and thesecond time comprises at least 5 months of the maintenance phase of theoral immunotherapy schedule.
 70. The method of claim 53, wherein thetime period of the oral immunotherapy schedule that is between the firsttime and the second time comprises at least 6 months of the maintenancephase of the oral immunotherapy schedule.
 71. The method of claim 53,wherein the time period of the oral immunotherapy schedule that isbetween the first time and the second time comprises at least 12 monthsof the maintenance phase of the oral immunotherapy schedule.
 72. Themethod of claim 53, wherein the oral immunotherapy schedule furthercomprises an initial escalation phase.